Recent progress on the effects of microRNAs and natural products on tumor epithelial–mesenchymal transition

Figures & data

Table 1 miRNAs known to inhibit EMT

miRNA suppressing EMT	Target	Cancer types	References
miR-145	ZEB2	Prostate cancer	^Citation22
miR-192	ZEB2	Multiple myeloma	^Citation25
miR-138	ZEB2, SNAIL2, vimentin, EZH2	Head and neck squamous cell carcinoma	^Citation26
miR-155	ZEB1, Smad	Lung cancer	^Citation33
	TWIST1, TCF4, VIM-1, ZEB2	Breast cancer	^Citation57
miR-200
miR-200a	ZEB1	Pancreatic cancer	^Citation37
miR-200b	ZEB, MMP-2/9	Bladder cancer	^Citation39
	Rho, Foxf2	Breast cancer, lung cancer	^Citation27, ^Citation32
miR-200c	ZEB1, CtBP	Pancreatic cancer	^Citation36
miR-141	ZEB1, CtBP	Pancreatic cancer	^Citation36
	MMP-2/9	Bladder cancer	^Citation39
miR-429	ZEB1, CRKL	Breast cancer	^Citation30
miR-147	ZEB1	Lung cancer, colorectal cancer	^Citation31
miR-451	SNAIL, C-MYC	Lung cancer, hepatocellular carcinoma	^Citation35, ^Citation46
miR-655	ZEB1, TGFBR2	Esophageal squamous cell carcinoma	^Citation38
miR-34
miR-34a	SNAIL, ZEB1, SLUG	Breast cancer, lung cancer, prostate	^Citation40, ^Citation42
miR-34b	LEF-1, β-catenin, Axin2	cancer, colon cancer
miR-34c
miR-29b	SNAIL, MMP-2	Prostate cancer, hepatocellular carcinoma	^Citation48, ^Citation53
miR-186	TWIST	Prostate cancer	^Citation59
miR-23a-3p	E-CAD	Prostate cancer	^Citation60
miR-22	SNAIL, MMP14	Gastroenteric tumor	^Citation52
miR-449a	MET, FOS	Hepatocellular carcinoma	^Citation47
LET-7	SNAIL	Hepatocellular carcinoma	^Citation49
miR-30a	SNAIL1	Lung cancer, hepatocellular carcinoma	^Citation50
miR-30c	Vimentin, fibronectin	Lung cancer, hepatocellular carcinoma	^Citation51
miRNA300	TWIST	Head and neck squamous cell carcinoma, breast cancer	^Citation54
miR-129-5p	TWIST, SNAIL	Breast cancer	^Citation55
miR-33b	TWIST1, HMGA2, SNAIL	Breast cancer	^Citation56
miR-106a	TWIST	Hepatocellular carcinoma	^Citation58
miR-33a, miR-32	TWIST1	Lung cancer	^Citation61, ^Citation62

Abbreviations: CRKL, Crk-like protein; CtBP, C-terminal-binding protein; E-CAD, E-cadherin; EMT, epithelial–mesenchymal transition; EZH2, enhancer of zeste homolog 2; FOS, FBJ murine osteosarcoma viral oncogene homolog; Foxf2, forkhead box F2; HMGA2, high-mobility group AT-hook2; MET, pro-oncogene, receptor tyrosine kinase; MMP, matrix metalloproteinases; TCF4, transcription factor 4; TGFBR2, transforming growth factor beta receptor 2; LEF-1, Lymphoid enhancer-binding factor 1; VIM, vimentin.

Table 2 miRNAs known to promote EMT

miRNA promoting EMT	Target	Cancer types	References
miR-9	E-CAD	Esophageal squamous cell carcinoma, colon cancer	^Citation63, ^Citation64
	KLF17	Hepatocellular carcinoma	^Citation65
miR-373	HIF-1α – TWIST	Breast cancer	^Citation67
miR-221	ATXN1	Breast cancer	^Citation68
miR-214	Sufu	Lung cancer	^Citation71
miR-346	XPC, SNAIL	Lung cancer	^Citation72
miR-21	PTEN, hSulf-1	Hepatocellular carcinoma, cholangiocarcinoma, clear cell renal cell carcinoma	^Citation73^–^Citation75
miR-181a	PTEN	Hepatocellular carcinoma	^Citation77

Abbreviations: E-CAD, E-cadherin; EMT, epithelial–mesenchymal transition; Fbxo45, atypical ubiquitin E3 ligase complex; HIF-1α, hypoxia-inducible factor; hSulf-1, human sulfate-1; KLF17, Krüppel-like factor 17; PTEN, phosphatase and tensin homolog deleted on chromosome ten; Sufu, suppressor-of-fused protein; XPC, xeroderma pigmentosum complementation group C.

Table 3 Natural products known to regulate EMT

Natural products	Mechanism	Cancer types	Cell lines	References
Curcumin	c-MET/PI3K/Akt/mTOR↓	Lung cancer	A549, PC9	^Citation87
	β-catenin, Slug↓	Breast cancer	MCF-7, T47D	^Citation88
	Erk1, AKT, TWIST↓	Breast cancer	MDA-MB-231 (ERα^+ or ERα^−)	^Citation89
	Fra-1, ZEB↓		NIH3T3	^Citation92
	NF-kB↓	Cholangiocarcinoma	HuCCT-1, TFK-1, HuH28	^Citation94
	miR-33b↑	Melanoma	Lu1205, A375	^Citation95
	Shh-GL11 pathway↓	Pancreatic cancer	PANC-1	^Citation97
	PI3K/AKT/NF-kB↓	Pancreatic cancer	PANC-1	^Citation98
	miR-26a, miR-101, miR-146a, miR-200b, miR-200c, LET-7 family↑	Pancreatic cancer	BxPC-3, MIAPaCa AsPC-1, MiaPaCa-2	^Citation99^–^Citation103
	miR-21, miR-221↓		PC-3
	Wnt pathway↓	Colon cancer	SW620	^Citation104
	miR-200b, c, 141, 429, 101↑	Colon cancer	HCT116, SW480	^Citation105
Genistein		Laryngocarcinoma	HEP-2	^Citation107
	miR-200b↑	Pancreatic cancer	ASPC-1	^Citation108
	miR-223↓	Pancreatic cancer	AsPC-1, PANC-1	^Citation109
	Wnt↓	Prostate cancer	ARCaP-E, ARCaP-M	^Citation110
	miR-145, miR-29a↑	Prostate cancer	PC-3	^Citation111
	miR-222, miR-221, miR-151↓
	TGF-β pathway↓	Ovarian cancer	BG-1	^Citation112
	NF-kB↓	Colon cancer	THP-1, HCT116	^Citation113
Resveratrol	ZEB2↓	Head and neck cancer		^Citation114
	NF-kB↓	Melanoma	K1735	^Citation115
	TGF-β/Smad↓	Breast cancer	MCF-7TR	^Citation116
	TWIST, SNAIL, ZEB↓	Lung cancer	A549	^Citation117
	HIF-1↓	Osteosarcoma	Saos-2	^Citation118
	miR-21↓	Hepatocellular carcinoma	SMMC7721, HepG2	^Citation119
	PTEN↑
	TGF-β/Smad↓	Colon cancer	LoVo	^Citation120
	NF-kB↓	Colon cancer	HCT116	^Citation121
	ERK-1/2, AKT, Androgen, IGFsR↓	Prostate cancer		^Citation122
	STAT3, Notch, NF-kB↓	Cervical adenocarcinoma	Hela	^Citation123
EGCG	miR-204↑	Oral squamous cell carcinoma	OECM1	^Citation125
	PI3K/AKT/mTOR↓	Breast cancer	MDA-MB-231	^Citation127
	HBP1, Wnt/β-catenin↓	Breast cancer	MDA-MB-231	^Citation128
	Smad2,3↓	Lung cancer	A549	^Citation129
	Erk5↓	Gastric cancer		^Citation130
	Notch↓	Colon cancer	HCT116, SW480	^Citation131
	miR-34a, miR-145, miR-200c↑		HCT116, SW480	^Citation131
Luteotin	PI3K/AKT/NF-kB↓	Lung cancer	A549	^Citation132
	β3 integrin↓	Malignant melanoma	B16F10	^Citation133
	STAT3, MMP2/7/9	Pancreatic cancer	PANC-1, SW1990	^Citation135
Cucurbitacin	Wnt/β-catenin↓	Lung cancer	A549, H1299	^Citation136
Apigenin	NF-kB, SNAIL↓	Hepatocellular carcinoma	PLC, Bel7402	^Citation137
Mang-NPs	Shh pathway, Slug↓	Pancreatic cancer	AsPC-1, PANC-1	^Citation138
Tripterine	NF-kB, SNAIL↓	Colon cancer	HCT116, HT-29	^Citation139
Osthole	SNAIL, E-CAD, miR-23a-3p↓	Prostate cancer	PC3, DU145	^Citation60

Abbreviations: E-CAD, E-cadherin; EGCG, epigallocatechin-3-gallate; EMT, epithelial–mesenchymal transition; HBP1, HMG-box transcription factor 1; NF-kB, nuclear factor kappa B; Shh, sonic hedgehog.

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