The p53/microRNA connection in gastrointestinal cancer

Figures & data

Figure 1 Incidence (A) and mortality (B) of indicated gastrointestinal (GI) cancers worldwide. (C) Prevalence of mutations in the TP53 gene in the indicated GI cancers.

Figure 2 Effects of p53 on miRNA biogenesis.

Notes: Wild-type p53 (green) regulates miRNA transcription, processing, and target selection. In contrast, mutant p53 (blue) is unable to induce the expression of miRNAs and additionally inhibits the p63-mediated activation of the miRNA processing protein Dicer.
Abbreviations: mRNA, messenger RNA; miRNA, microRNA; pre-microRNA, miRNA precursor molecule; pri-microRNA, primary miRNA; miRISC, miRNA-induced silencing complex; mut, mutant; RE, response element.

Table 1 Summary of changes in expression of p53-pathway-related miRNAs in GI cancers

Table 2 Compilation of p53-regulated miRNAs and their alterations in GI cancers

miRNA	Validated by	Clinical and pathological associations in GI cancers
miRNAs induced by p53
miR-34a	Luc reporter (mut), qPCR, ChIP^Citation24	CRC: downregulated in tumors^Citation38 and serum;^Citation162 Downregulation in metastatic tumors;^Citation70,Citation163 CpG methylation^Citation66,Citation67 in metastatic tumors^Citation70
		EC, HCC: downregulated in tumors;^Citation39,Citation41 CpG methylation^Citation39,Citation41,Citation164
		GC: downregulated in tumors^Citation40
		PaC: downregulation associated with poor OS;^Citation165 CpG methylation^Citation66,Citation67
miR-34b/c	Luc reporter (mut), qPCR, ChIP^Citation24	CRC, GC, PaC: CpG methylation^Citation67,Citation69
		EC: upregulation associated with advanced tumor stage;^Citation166 CpG methylation^Citation164
		HCC: downregulated in tumors^Citation41
miR-15a/16-1	qPCR, ChIP^Citation33	CRC: miR-16-1 down-regulated in tumors;^Citation77 Downregulation of miR-16-1 associated with pN, TNM stage, and poor OS^Citation77
		EC: miR-15a upregulated in tumors^Citation167
miR-200c/141	Luc reporter (mut), qPCR, ChIP^Citation32	CRC: downregulation of miR-200c is associated with poor OS;^Citation168 miR-200c is downregulated in metastatic CRC;^Citation169 miR-200c is upregulated in patient serum;^Citation112,Citation170 Upregulation in serum is associated with tumor stage, pN, metastasis, and prognosis;^Citation109 CpG methylation^Citation171
		EC: miR-200c is upregulated in patient serum;^Citation108 Upregulation in serum associated with poor RFS^Citation108
		GC: miR-141 is downregulated in tumors^Citation172
		HCC: miR-200c is downregulated in tumors;^Citation173 Downregulation associated with poor RFS^Citation174
miR-200a/200b/429	Luc reporter (mut), qPCR, ChIP^Citation32	CRC: miR-429 is downregulated in tumors^Citation175; downregulation of miR-200a/429 is associated with poor OS;^Citation168 CpG methylation^Citation171
		EC: miR-200a/b are upregulated in tumors^Citation167,Citation176
		GC: miR-200a is downregulated in tumors^Citation176
		PaC: CpG hypomethylation and overexpression in tumors^Citation177
miR-107	Luc reporter (mut), qPCR, ChIP^Citation36	CRC: upregulation associated with metastasis and poor OS^Citation117
		EC: downregulated in tumors and serum^Citation178
		GC: upregulated in tumors; Upregulation associated with tumor invasion, stage, pN, and poor DFS and OS^Citation119
		PaC: CpG methylation^Citation179
miR-145	Luc reporter (mut), qPCR, ChIP^Citation35	CRC: downregulated in tumors^Citation180,Citation181 and patient stool samples;^Citation182 Downregulation associated with tumor size^Citation91
		EC, GC, HCC, PaC: downregulated in tumors^Citation88^–^Citation90,Citation173,Citation183,Citation184
miR-192/194/215	qPCR, ChIP^Citation34	CRC: downregulation of miR-192/194/215 in tumors;^Citation34,Citation185,Citation186 Downregulation of miR-192/215 associated with stage, grade, pN;^Citation103,Citation186 Downregulation of miR-215 associated with poor RFS;^Citation101 Upregulation of miR-194 associated with poor RFS and OS^Citation187
		GC: downregulation of miR-194 associated with higher tumor size and stage;^Citation188 miR-215 upregulated in tumors^Citation189
miR-29	Luc reporter, qPCR^Citation149	CRC: upregulated in serum;^Citation190 Upregulation associated with metastasis and OS^Citation191
		GC: downregulated in tumors; Downregulation associated with metastasis^Citation152,Citation192
		HCC: downregulated in tumors; Downregulation associated with poor RFS and OS^Citation153,Citation154
miR-605	Luc reporter (mut), qPCR, ChIP^Citation193	NA
miR-149	Luc reporter (mut), qPCR, ChIP^Citation194	CRC: downregulated in tumors;^Citation195 CpG methylation;^Citation196 Downregulation associated with invasion and poor OS^Citation196
		GC: downregulated in tumors^Citation197
miR-22	Luc reporter (mut), qPCR, ChIP^Citation198	CRC: downregulated in tumors and liver metastases; Downregulation associated with poor OS^Citation199
		EC, PaC: upregulated in serum^Citation200,Citation201
		GC: downregulated in tumors;^Citation202 Downregulation associated with tumor stage, pN, metastasis, poor OS^Citation203
		HCC: downregulated in tumors, Downregulation associated with pN, grade, and poor OS^Citation204,Citation205
miR-23b	Luc reporter (mut), ChIP^Citation206	EC: downregulation associated with poor prognosis^Citation207
		CRC, HCC: downregulated in tumors^Citation208,Citation209
miR-205	Luc reporter (mut), qPCR, ChIP^Citation210	EC: downregulated in tumors,^Citation211,Citation212 Down-regulation associated with poor prognosis^Citation207
		HCC: downregulated in tumors^Citation213
miR-1246	Luc reporter (mut), qPCR, ChIP^Citation214	CRC: downregulated in tumors^Citation215; Upregulated in patient serum^Citation216
		EC: upregulated in tumors^Citation217 and patient serum^Citation218
miR-1204	qPCR, ChIP^Citation219	NA
miRNAs repressed by p53
miR-17-92	Luc reporter (mut), qPCR, ChIP^Citation126	CRC,^Citation220,Citation221 EC,^Citation222,Citation223 GC,^Citation224,Citation225 HCC,^Citation226 PaC;^Citation227 Upregulated in tumors
miR-224	Luc reporter (mut), qPCR, ChIP^Citation124	CRC: upregulated in tumors;^Citation228,Citation229 Upregulation associated with poor RFS and OS;^Citation228,Citation229 Downregulation associated with poor OS;^Citation230 Upregulation associated with tumor size, stage, and metastasis^Citation229
		HCC: upregulated in tumors^Citation231,Citation232
miR-502	Luc reporter^Citation125	CRC: downregulated in tumors^Citation125

Abbreviations: ChIP, chromatin immunoprecipitation; CRC, colorectal cancer; DFS, disease-free survival; EC, esophageal cancer; GC, gastric cancer; GI, gastrointestinal; HCC, hepatocellular cancer; Luc reporter, Luciferase miRNA promoter reporter assay; miRNA, microRNA; mut, mutation in the p53 binding site; NA, not applicable or not analyzed; OS, overall survival; PaC, pancreatic cancer; pN, nodal status; qPCR, quantitative real-time polymerase chain reaction; RFS, relapse-free survival; TNM, tumor, node, metastasis status based classification.

Table 3 Compilation of miRNAs that directly target p53 and their alterations in GI cancers

miRNA	Validated by	Clinical and pathological associations in GI cancers
miR-25	Luc reporter (mut), qPCR, WB^Citation134	CRC: upregulated in tumors; Upregulation associated with invasion, metastasis, poor OS^Citation146
		EC: upregulated in tumors and serum;^Citation233 Upregulation associated with pN and tumor stage^Citation137,Citation145
		GC: upregulated in serum^Citation234 and tumors;^Citation235 Upregulation associated with tumor progression^Citation236,Citation237
miR-30d	Luc reporter (mut), qPCR, WB^Citation134	CRC, PaC: gene amplification^Citation148
		HCC: upregulated in tumors; Upregulation associated with metastasis^Citation238
miR-33	Luc reporter (mut), WB^Citation135	NA
miR-98	Luc reporter (mut), WB^Citation143	EC: downregulated in tumors; Downregulation associated with tumor stage and pN^Citation239
miR-125a	Luc reporter (mut), WB^Citation142	EC: downregulation associated with tumor progression^Citation240
		GC: downregulation associated with invasion, metastasis, poor OS^Citation240^–^Citation242
		HCC: downregulated in tumors; Downregulation associated with tumor stage and metastasis^Citation243,Citation244
miR-125b	Luc reporter (mut), WB^Citation129	CRC: upregulation associated with tumor size, invasion, poor OS^Citation241
		EC: downregulation associated with tumor progression^Citation240
		GC: upregulation associated with tumor progression;^Citation236 Downregulation associated with tumor progression^Citation240
		HCC: upregulated in serum;^Citation131 Downregulated in tumors^Citation244,Citation245
		PaC: upregulated in tumors^Citation246
miR-150	Luc reporter (mut), WB^Citation138	CRC: downregulated in tumors; Downregulation associated with poor OS^Citation247
		EC: downregulated in tumors; Downregulation associated with invasion, metastasis, and poor OS^Citation248
		GC: upregulated in tumors^Citation249
		PaC: downregulated in tumors^Citation250
miR-214	Luc reporter (mut), WB^Citation141	CRC: upregulation associated with poor OS^Citation236
		EC: upregulated in tumors;^Citation251 Downregulated in tumors^Citation239
		GC: upregulated in tumors; Upregulation associated with poor OS^Citation252
		HCC: downregulated in tumors; Downregulation associated with poor RFS and OS^Citation253^–^Citation255
		PaC: upregulated in tumors^Citation78
miR-375	Luc reporter (mut), WB^Citation139	EC: downregulated in tumors and serum; Downregulation associated with poor OS^Citation145
		PaC: downregulated in tumors^Citation236
miR-380	Luc reporter, WB^Citation136	NA
miR-504	Luc reporter (mut), WB^Citation133	NA
miR-1285	Luc reporter (mut), qPCR, WB^Citation140	NA

Abbreviations: CRC, colorectal cancer; EC, esophageal cancer; GC, gastric cancer; GI, gastrointestinal; HCC, hepatocellular cancer; Luc reporter, Luciferase reporter assay with p53 3′-UTR; miRNA, microRNA; mut, mutation in the miRNA seed sequence; NA, not applicable or not analyzed; OS, overall survival; PaC, pancreatic cancer; pN, nodal status; qPCR, quantitative real-time polymerase chain reaction; RFS, relapse free survival; WB, Western blot.

Figure 3 The role of p53/miRNA axis in (A) p53 autoregulation, (B) cancer cell metabolism, (C) invasion, and metastasis, as a result of the regulation of EMT/MET (D) cancer-associated inflammatory signaling.

Notes: Color code: p53/green; miRNAs/yellow; miRNA-targets/red; green arrow/activation; red arrow/inhibition.
Abbreviations: EMT, epithelial–mesenchymal transition; IL-6, interleukin 6; IL-6R, interleukin 6 receptor; MET, mesenchymal–epithelial transition; miRNA, microRNA; NAD⁺, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase.

HeLHeXLimLPA microRNA component of the p53 tumour suppressor networkNature200744771481130113417554337

 PubMed Web of Science ®Google Scholar

RoySLeviEMajumdarAPSarkarFHExpression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDFJ Hematol Oncol201255822992310

 PubMed Web of Science ®Google Scholar

NugentMMillerNKerinMJCirculating miR-34a levels are reduced in colorectal cancerJ Surg Oncol2012106894795222648208

 PubMed Web of Science ®Google Scholar

SiemensHNeumannJJackstadtRDetection of miR-34a promoter methylation in combination with elevated expression of c-Met and β-catenin predicts distant metastasis of colon cancerClin Cancer Res201319371072023243217

 PubMed Web of Science ®Google Scholar

WuJWuGLvLMicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1Carcinogenesis201233351952822198213

 PubMed Web of Science ®Google Scholar

LodyginDTarasovVEpanchintsevAInactivation of miR-34a by aberrant CpG methylation in multiple types of cancerCell Cycle20087162591260018719384

 PubMed Web of Science ®Google Scholar

VogtMMundingJGrünerMFrequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomasVirchows Arch2011458331332221225432

 PubMed Web of Science ®Google Scholar

CuiXZhaoZLiuDInactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinomaJ Exp Clin Cancer Res2014332024528540

 PubMed Web of Science ®Google Scholar

XieKLiuJChenJMethylation-associated silencing of microRNA-34b in hepatocellular carcinoma cancerGene2014543110110724704024

 PubMed Web of Science ®Google Scholar

ChenXHuHGuanXCpG island methylation status of miRNAs in esophageal squamous cell carcinomaInt J Cancer201213071607161321547903

 PubMed Web of Science ®Google Scholar

StánitzEJuhászKTóthCGombosKNataliPGEmberIEvaluation of MicroRNA expression pattern of gastric adenocarcinoma associated with socioeconomic, environmental and lifestyle factors in northwestern HungaryAnticancer Res20133383195320023898078

 PubMed Web of Science ®Google Scholar

JamiesonNBMorranDCMortonJPMicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinomaClin Cancer Res201218253454522114136

 PubMed Web of Science ®Google Scholar

SuzukiHYamamotoENojimaMMethylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defectCarcinogenesis201031122066207320924086

 PubMed Web of Science ®Google Scholar

HarataKIshiguroHKuwabaraYKimuraMMitsuiAMicroRNA-34b has an oncogenic role in esophageal squamous cell carcinomaOncol Lett20101468568922966364

 PubMed Web of Science ®Google Scholar

FabbriMBottoniAShimizuMAssociation of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemiaJAMA20113051596721205967

 PubMed Web of Science ®Google Scholar

QianJJiangBLiMChenJFangMPrognostic significance of microRNA-16 expression in human colorectal cancerWorld J Surg201337122944294924045965

 PubMed Web of Science ®Google Scholar

LiuSGQinXGZhaoBSDifferential expression of miRNAs in esophageal cancer tissueOncol Lett2013551639164223761828

 PubMed Web of Science ®Google Scholar

KimTVeroneseAPichiorriFp53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2J Exp Med2011208587588321518799

 PubMed Web of Science ®Google Scholar

DiazTTejeroRMorenoIRole of miR-200 family members in survival of colorectal cancer patients treated with fluoropyrimidinesJ Surg Oncol2014109767668324510588

 PubMed Web of Science ®Google Scholar

HurKToiyamaYTakahashiMMicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasisGut20136291315132622735571

 PubMed Web of Science ®Google Scholar

ZhangGJZhouTLiuZLTianHPXiaSSPlasma miR-200c and miR-18a as potential biomarkers for the detection of colorectal carcinomaMol Clin Oncol20131237938424649179

 PubMedGoogle Scholar

ChenJWangWZhangYChenYHuTPredicting distant metastasis and chemoresistance using plasma miRNAsMed Oncol201431179924310813

 PubMed Web of Science ®Google Scholar

ToiyamaYHurKTanakaKSerum miR-200c Is a Novel Prognostic and Metastasis-Predictive Biomarker in Patients With Colorectal CancerAnn Surg2014259473574323982750

 PubMed Web of Science ®Google Scholar

DavalosVMoutinhoCVillanuevaADynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesisOncogene201231162062207421874049

 PubMed Web of Science ®Google Scholar

TanakaKMiyataHYamasakiMCirculating miR-200c levels significantly predict response to chemotherapy and prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancerAnn Surg Oncol201320Suppl 3S607S61523838916

 PubMed Web of Science ®Google Scholar

DuYXuYDingLDown-regulation of miR-141 in gastric cancer and its involvement in cell growthJ Gastroenterol200944655656119363643

 PubMed Web of Science ®Google Scholar

KarakatsanisAPapaconstantinouIGazouliMLyberopoulouAPolymeneasGVorosDExpression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significanceMol Carcinog201352429730322213236

 PubMed Web of Science ®Google Scholar

YehTSWangFChenTCExpression profile of microRNA-200 family in hepatocellular carcinoma with bile duct tumor thrombusAnn Surg2014259234635424135722

 PubMed Web of Science ®Google Scholar

SunYShenSLiuXMiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinomaMol Cell Biochem20143901-2193024402783

 PubMed Web of Science ®Google Scholar

ChenZSaadRJiaPGastric adenocarcinoma has a unique microRNA signature not present in esophageal adenocarcinomaCancer2013119111985199323456798

 PubMed Web of Science ®Google Scholar

LiAOmuraNHongSMPancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levelsCancer Res201070135226523720551052

 PubMed Web of Science ®Google Scholar

BöhligLFriedrichMEngelandKp53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteinsNucleic Acids Res201139244045320833636

 PubMed Web of Science ®Google Scholar

ChenHYLinYMChungHCmiR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4Cancer Res201272143631364122593189

 PubMed Web of Science ®Google Scholar

SharmaPSarayaAGuptaPSharmaRDecreased levels of circulating and tissue miR-107 in human esophageal cancerBiomarkers201318432233023627613

 PubMed Web of Science ®Google Scholar

InoueTIinumaHOgawaEInabaTFukushimaRClinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancerOncol Rep20122761759176422407237

 PubMed Web of Science ®Google Scholar

LeeKHLottermanCKarikariCEpigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancerPancreatology20099329330119407485

 PubMed Web of Science ®Google Scholar

SachdevaMZhuSWuFp53 represses c-Myc through induction of the tumor suppressor miR-145Proc Natl Acad Sci U S A200910693207321219202062

 PubMed Web of Science ®Google Scholar

FengYZhuJOuCMicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1Br J Cancer201411092300230924642628

 PubMed Web of Science ®Google Scholar

EarleJSLuthraRRomansAAssociation of microRNA expression with microsatellite instability status in colorectal adenocarcinomaJ Mol Diagn201012443344020413677

 PubMed Web of Science ®Google Scholar

LiJMZhaoRHLiSTDown-regulation of fecal miR-143 and miR-145 as potential markers for colorectal cancerSaudi Med J2012331242922273643

 PubMed Web of Science ®Google Scholar

SlabyOSvobodaMFabianPAltered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancerOncology2007725–639740218196926

 PubMed Web of Science ®Google Scholar

KanoMSekiNKikkawaNmiR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinomaInt J Cancer2010127122804281421351259

 PubMed Web of Science ®Google Scholar

PapaconstantinouIGMantaAGazouliMExpression of microR-NAs in patients with pancreatic cancer and its prognostic significancePancreas2013421677122850622

 PubMed Web of Science ®Google Scholar

QiuTZhouXWangJMiR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancerFEBS Lett201458871168117724613927

 PubMed Web of Science ®Google Scholar

XingAYWangBShiDBDeregulated expression of miR-145 in manifold human cancer cellsExp Mol Pathol2013951919723714355

 PubMed Web of Science ®Google Scholar

BraunCJZhangXSavelyevaIp53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrestCancer Res20086824100941010419074875

 PubMed Web of Science ®Google Scholar

ChiangYSongYWangZmicroRNA-192, -194 and -215 are frequently downregulated in colorectal cancerExp Ther Med20123356056622969930

 PubMed Web of Science ®Google Scholar

FaltejskovaPSvobodaMSrutovaKIdentification and functional screening of microRNAs highly deregulated in colorectal cancerJ Cell Mol Med201216112655266622469014

 PubMed Web of Science ®Google Scholar

GengLChaudhuriATalmonGMicroRNA-192 suppresses liver metastasis of colon cancerOncogene Epub November 11, 2013

 Web of Science ®Google Scholar

LiSGaoJGuJYuanJHuaDShenLMicroRNA-215 inhibits relapse of colorectal cancer patients following radical surgeryMed Oncol201330254923532818

 PubMed Web of Science ®Google Scholar

KahlertCKluppFBrandKInvasion front-specific expression and prognostic significance of microRNA in colorectal liver metastasesCancer Sci2011102101799180721722265

 PubMed Web of Science ®Google Scholar

SongYZhaoFWangZInverse association between miR-194 expression and tumor invasion in gastric cancerAnn Surg Oncol201219Suppl 3S509S51721845495

 PubMed Web of Science ®Google Scholar

DengYHuangZXuYMiR-215 modulates gastric cancer cell proliferation by targeting RB1Cancer Lett20143421273523981575

 PubMed Web of Science ®Google Scholar

UgaldeAPRamsayAJde la RosaJAging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53EMBO J201130112219223221522133

 PubMed Web of Science ®Google Scholar

WangLGGuJSerum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasisCancer Epidemiol2012361e61e6722018950

 PubMed Web of Science ®Google Scholar

TangWZhuYGaoJMicroRNA-29a promotes colorectal cancer metastasis by regulating matrix metalloproteinase 2 and E-cadherin via KLF4Br J Cancer2014110245045824281002

 PubMed Web of Science ®Google Scholar

GongJLiJWangYCharacterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancerCarcinogenesis201435249750624130168

 PubMed Web of Science ®Google Scholar

ChenLXiaoHWangZ-HmiR-29a suppresses growth and invasion of gastric cancer cells in vitro by targeting VEGF-ABMB Rep2014471394424209632

 PubMed Web of Science ®Google Scholar

ZhuH-TDongQ-ZShengY-YMicroRNA-29a-5p is a novel predictor for early recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resectionPLoS One2012712e5239323285022

 PubMed Web of Science ®Google Scholar

XiongYFangJHYunJPEffects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinomaHepatology201051383684520041405

 PubMed Web of Science ®Google Scholar

XiaoJLinHLuoXLuoXWangZmiR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stressEMBO J201130352453221217645

 PubMed Web of Science ®Google Scholar

JinLHuWLJiangCCMicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanomaProc Natl Acad Sci U S A201110838158401584521896753

 PubMed Web of Science ®Google Scholar

ØsterBLinnetLChristensenLLCOLOFOL steering groupNon-CpG island promoter hypomethylation and miR-149 regulate the expression of SRPX2 in colorectal cancerInt J Cancer2013132102303231523115050

 PubMed Web of Science ®Google Scholar

WangFMaYLZhangPSP1 mediates the link between methy-lation of the tumour suppressor miR-149 and outcome in colorectal cancerJ Pathol20132291122422821729

 PubMed Web of Science ®Google Scholar

WangYZhengXZhangZMicroRNA-149 inhibits proliferation and cell cycle progression through the targeting of ZBTB2 in human gastric cancerPLoS One2012710e4169323144691

 PubMed Web of Science ®Google Scholar

LinJHuoRXiaoLA novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritisArthritis Rheumatol2014661495924449575

 PubMed Web of Science ®Google Scholar

ZhangGXiaSTianHLiuZZhouTClinical significance of miR-22 expression in patients with colorectal cancerMed Oncol20122953108311222492279

 PubMed Web of Science ®Google Scholar

ZhangCWangCChenXExpression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinomaClin Chem201056121871187920943850

 PubMed Web of Science ®Google Scholar

GanepolaGARutledgeJRSumanPYiengpruksawanAChangDHNovel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancerWorld J Gastrointest Oncol201461223324578785

 PubMed Web of Science ®Google Scholar

GuoMMHuLHWangYQmiR-22 is down-regulated in gastric cancer, and its overexpression inhibits cell migration and invasion via targeting transcription factor Sp1Med Oncol201330254223529765

 PubMed Web of Science ®Google Scholar

WangWLiFZhangYTuYYangQGaoXReduced expression of miR-22 in gastric cancer is related to clinicopathologic characteristics or patient prognosisDiagn Pathol2013810223786758

 PubMed Web of Science ®Google Scholar

ZhouLHeJZhangYMicroRNA-22 expression in hepatocellular carcinoma and its correlation with ezrin proteinJ Int Med Res20134141009101623766411

 PubMed Web of Science ®Google Scholar

ZhangJYangYYangTmicroRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicityBr J Cancer201010381215122020842113

 PubMed Web of Science ®Google Scholar

Au YeungCLTsangTYYauPLKwokTTHuman papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathwayOncogene201130212401241021242962

 PubMed Web of Science ®Google Scholar

ZhaoBSLiuSGWangTYScreening of microRNA in patients with esophageal cancer at same tumor node metastasis stage with different prognosesAsian Pac J Cancer Prev201314113914323534712

 PubMedGoogle Scholar

SalviASabelliCMonciniSMicroRNA-23b mediates uroki-nase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cellsFEBS J2009276112966298219490101

 PubMed Web of Science ®Google Scholar

ZhangHHaoYYangJGenome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasisNat Commun2011255422109528

 PubMed Web of Science ®Google Scholar

PiovanCPalmieriDDi LevaGOncosuppressive role of p53-induced miR-205 in triple negative breast cancerMol Oncol20126445847222578566

 PubMed Web of Science ®Google Scholar

GuJWangYWuXMicroRNA in the pathogenesis and prognosis of esophageal cancerCurr Pharm Des20131971292130023092349

 PubMed Web of Science ®Google Scholar

SaadRChenZZhuSDeciphering the unique microRNA signature in human esophageal adenocarcinomaPLoS One201385e6446323724052

 PubMed Web of Science ®Google Scholar

ZhangTZhangJCuiMHepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesisNeoplasia201315111282129124339740

 PubMed Web of Science ®Google Scholar

ZhangYLiaoJMZengSXLuHp53 downregulates Down syndrome-associated DYRK1A through miR-1246EMBO Rep201112881181721637297

 PubMed Web of Science ®Google Scholar

PiepoliATavanoFCopettiMMirna expression profiles identify drivers in colorectal and pancreatic cancersPLoS One201273e3366322479426

 PubMed Web of Science ®Google Scholar

Ogata-KawataHIzumiyaMKuriokaDCirculating exosomal microRNAs as biomarkers of colon cancerPLoS One201494e9292124705249

 PubMed Web of Science ®Google Scholar

FuHLWu dePWangXFAltered miRNA expression is associated with differentiation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) in patients from Huaian, ChinaCell Biochem Biophys201367265766823516093

 PubMed Web of Science ®Google Scholar

TakeshitaNHoshinoIMoriMSerum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinomaBr J Cancer2013108364465223361059

 PubMed Web of Science ®Google Scholar

BarsottiAMBeckermanRLaptenkoOHuppiKCaplenNJPrivesCp53-Dependent induction of PVT1 and miR-1204J Biol Chem201228742509251922110125

 PubMed Web of Science ®Google Scholar

YanHLXueGMeiQRepression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosisEMBO J200928182719273219696742

 PubMed Web of Science ®Google Scholar

KogaYYasunagaMTakahashiAMicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screeningCancer Prev Res (Phila)20103111435144220959518

 PubMed Web of Science ®Google Scholar

DiosdadoBvan de WielMATerhaar Sive DrosteJSMiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progressionBr J Cancer2009101470771419672269

 PubMed Web of Science ®Google Scholar

XuXLJiangYHFengJGSuDChenPCMaoWMMicroRNA-17, microRNA-18a, and microRNA-19a are prognostic indicators in esophageal squamous cell carcinomaAnn Thorac Surg20149731037104524360091

 PubMed Web of Science ®Google Scholar

LiuMWangZYangSTNF-alpha is a novel target of miR-19aInt J Oncol20113841013102221271217

 PubMed Web of Science ®Google Scholar

TsujiuraMKomatsuSIchikawaDCirculating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancerGastric Cancer Epub March 14, 2014

 Web of Science ®Google Scholar

ShiotaniAUedoNIishiHH. pylori eradication did not improve dysregulation of specific oncogenic miRNAs in intestinal metaplastic glandsJ Gastroenterol201247998899822382634

 PubMed Web of Science ®Google Scholar

ShigokaMTsuchidaAMatsudoTDeregulation of miR-92a expression is implicated in hepatocellular carcinoma developmentPathol Int201060535135720518884

 PubMed Web of Science ®Google Scholar

MorimuraRKomatsuSIchikawaDNovel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancerBr J Cancer2011105111733174022045190

 PubMed Web of Science ®Google Scholar

LiangMYaoGYinMTranscriptional cooperation between p53 and NF-κB p65 regulates microRNA-224 transcription in mouse ovarian granulosa cellsMol Cell Endocrinol20133701–211912923474441

 PubMed Web of Science ®Google Scholar

ZhangGJZhouHXiaoHXLiYZhouTUp-regulation of miR-224 promotes cancer cell proliferation and invasion and predicts relapse of colorectal cancerCancer Cell Int201313110424152489

 PubMed Web of Science ®Google Scholar

LiaoWTLiTTWangZGmicroRNA-224 promotes cell proliferation and tumor growth in human colorectal cancer by repressing PHLPP1 and PHLPP2Clin Cancer Res201319174662467223846336

 PubMed Web of Science ®Google Scholar

YuanKXieKFoxJDecreased levels of miR-224 and the passenger strand of miR-221 increase MBD2, suppressing maspin and promoting colorectal tumor growth and metastasis in miceGastroenterology20131454853864.e923770133

 PubMed Web of Science ®Google Scholar

SciscianiCVossioSGuerrieriFTranscriptional regulation of miR-224 upregulated in human HCCs by NFkappaB inflammatory pathwaysJ Hepatol201256485586122178270

 PubMed Web of Science ®Google Scholar

ZhangYTakahashiSTasakaAYoshimaTOchiHChayamaKInvolvement of microRNA-224 in cell proliferation, migration, invasion, and anti-apoptosis in hepatocellular carcinomaJ Gastroenterol Hepatol201328356557522989374

 PubMed Web of Science ®Google Scholar

ZhaiHSongBXuXZhuWJuJInhibition of autophagy and tumor growth in colon cancer by miR-502Oncogene201332121570157922580605

 PubMed Web of Science ®Google Scholar

KumarMLuZTakwiAANegative regulation of the tumor suppressor p53 gene by microRNAsOncogene201130784385320935678

 PubMed Web of Science ®Google Scholar

LiXYangCWangXZhangJZhangRLiuRThe expression of miR-25 is increased in colorectal cancer and is associated with patient prognosisMed Oncol201431178124293092

 PubMed Web of Science ®Google Scholar

KomatsuSIchikawaDHirajimaSPlasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinomaBr J Cancer2014

 Web of Science ®Google Scholar

XuXChenZZhaoXMicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinomaBiochem Biophys Res Commun2012421464064522450326

 PubMed Web of Science ®Google Scholar

WuCLiMHuCDuanHClinical significance of serum miR-223, miR-25 and miR-375 in patients with esophageal squamous cell carcinomaMol Biol Rep20144131257126624390317

 PubMed Web of Science ®Google Scholar

ZhuCRenCHanJA five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancerBr J Cancer201411092291229924595006

 PubMed Web of Science ®Google Scholar

ZhaoHWangYYangLJiangRLiWMiR-25 promotes gastric cancer cells growth and motility by targeting RECKMol Cell Biochem20143851–220721324078004

 PubMed Web of Science ®Google Scholar

UedaTVoliniaSOkumuraHRelation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysisLancet Oncol201011213614620022810

 PubMed Web of Science ®Google Scholar

KimBHHongSWKimAChoiSHYoonSOPrognostic implications for high expression of oncogenic microRNAs in advanced gastric carcinomaJ Surg Oncol2013107550551022996433

 PubMed Web of Science ®Google Scholar

LiNKaurSGreshockJA combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancerCancer Res201272115416422058146

 PubMed Web of Science ®Google Scholar

YaoJLiangLHuangSMicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinomaHepatology201051384685620054866

 PubMed Web of Science ®Google Scholar

Herrera-MerchanACerratoCLuengoGmiR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewalCell Cycle20109163277328520703086

 PubMed Web of Science ®Google Scholar

ZhangSZhangCLiYWangPYueZXieSmiR-98 regulates cisplatin-induced A549 cell death by inhibiting TP53 pathwayBiomed Pharmacother201165643644221880462

 PubMed Web of Science ®Google Scholar

HuangS-DYuanYZhuangC-WMicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinomaMol Cancer2012115122867052

 PubMed Web of Science ®Google Scholar

ZhangYGaoJSTangXMicroRNA 125a and its regulation of the p53 tumor suppressor geneFEBS Lett2009583223725373019818772

 PubMed Web of Science ®Google Scholar

FassanMPizziMRealdonSThe HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesisHum Pathol20134491804181023618359

 PubMed Web of Science ®Google Scholar

HashiguchiYNishidaNMimoriKDown-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significanceInt J Oncol20124051477148222322911

 PubMed Web of Science ®Google Scholar

BiQTangSXiaLEctopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGFPLoS One201276e4016922768249

 PubMed Web of Science ®Google Scholar

KimJKNohJHJungKHSirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125bHepatology20135731055106723079745

 PubMed Web of Science ®Google Scholar

LeMTTehCShyh-ChangNMicroRNA-125b is a novel negative regulator of p53Genes Dev200923786287619293287

 PubMed Web of Science ®Google Scholar

NishidaNMimoriKFabbriMMicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumabClin Cancer Res20111792725273321220473

 PubMed Web of Science ®Google Scholar

GirayBGEmekdasGTezcanSProfiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinomaMol Biol Rep20144174513451924595450

 PubMed Web of Science ®Google Scholar

LiangLWongC-MYingQMicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2Hepatology20105251731174020827722

 PubMed Web of Science ®Google Scholar

BloomstonMFrankelWLPetroccaFMicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitisJAMA2007297171901190817473300

 PubMed Web of Science ®Google Scholar

ZhangNWeiXXuLmiR-150 promotes the proliferation of lung cancer cells by targeting P53FEBS Lett2013587152346235123747308

 PubMed Web of Science ®Google Scholar

MaYZhangPWangFmiR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancerGut201261101447145322052060

 PubMed Web of Science ®Google Scholar

YokoboriTSuzukiSTanakaNMiR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1Cancer Sci20131041485423013135

 PubMed Web of Science ®Google Scholar

WuQJinHYangZMiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2Biochem Biophys Res Commun2010392334034520067763

 PubMed Web of Science ®Google Scholar

SrivastavaSKBhardwajASinghSMicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cellsCarcinogenesis201132121832183921983127

 PubMed Web of Science ®Google Scholar

XuCXXuMTanLMicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/NanogJ Biol Chem201228742349703497822927443

 PubMed Web of Science ®Google Scholar

ZhouYHongLPrediction value of miR-483 and miR-214 in prognosis and multidrug resistance of esophageal squamous cell carcinomaGenet Test Mol Biomarkers201317647047423721345

 PubMed Web of Science ®Google Scholar

YangTSYangXHWangXDWangYLZhouBSongZSMiR-214 regulate gastric cancer cell proliferation, migration and invasion by targeting PTENCancer Cell Int20131316823834902

 PubMed Web of Science ®Google Scholar

ShihTCTienYJWenCJMicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatomaJ Hepatol201257358459122613005

 PubMed Web of Science ®Google Scholar

WangJLiJWangXZhengCMaWDownregulation of microRNA-214 and overexpression of FGFR-1 contribute to hepatocellular carcinoma metastasisBiochem Biophys Res Commun20134391475323962428

 PubMed Web of Science ®Google Scholar

ZhangXJYeHZengCWHeBZhangHChenYQDysregulation of miR-15a and miR-214 in human pancreatic cancerJ Hematol Oncol201034621106054

 PubMed Web of Science ®Google Scholar

LiuYXingRZhangXmiR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cellsDNA Repair (Amst)201312974175023835407

 PubMed Web of Science ®Google Scholar

SwarbrickAWoodsSLShawAmiR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastomaNat Med201016101134114020871609

 PubMed Web of Science ®Google Scholar

HuWChanCSWuRNegative regulation of tumor suppressor p53 by microRNA miR-504Mol Cell201038568969920542001

 PubMed Web of Science ®Google Scholar

TianSHuangSWuSGuoWLiJHeXMicroRNA-1285 inhibits the expression of p53 by directly targeting its 3′ untranslated regionBiochem Biophys Res Commun2010396243543920417621

 PubMed Web of Science ®Google Scholar