Recent Advances in the Potential Use of Circular RNA for the Diagnosis and Treatment of Pancreatic Cancer

Figures & data

Table 1 CircRNAs in Pancreatic Cancer and Their Molecular Mechanisms as miRNA Sponge

CircRNA	Year	Expression	MiRNA Sponge	Signal Pathway	Ref.
circRNA_100782	2017	Upregulated	miR-124	IL6/STAT3	[^Citation64]
hsa_circ_0006215	2018	Upregulated	miR-378a-3p	SERPINA4	[^Citation44]
hsa_circ_0000977	2018	Upregulated	miR-874-3p	PLK1	[^Citation67]
	2019	Upregulated	miR-153	HIF1A/ADAM10	[^Citation68]
hsa_circ_0001649	2018	Downregulated	-	-	[^Citation71]
circ-IARS	2018	Upregulated	miR-122	RhoA/F-actin/ZO-1	[^Citation69]
hsa_circ_0099999 (circZMYM2)	2018	Upregulated	miR-335-5p	JMJD2C	[^Citation92]
hsa_circ_0036627 (circ-PDE8A)	2018	Upregulated	miR-338	MACC/MET/ERK	[^Citation93]
hsa_circ_0007334	2019	Upregulated	miR-144-3p	MMP7	[^Citation94]
			miR-577	COL1A1
circ_0030235	2019	Upregulated	miR-1253/miR-1294	-	[^Citation80]
circ-ASH2L	2019	Upregulated	miR-34a	Notch1	[^Citation95]
hsa_circ_0005397 (circRHOT1)	2019	Upregulated	miR-26b/miR-125a/miR-330/miR-382	-	[^Citation96]
	2020	Upregulated	miR-125a-3p	E2F3	[^Citation97]
circ-ADAM9	2019	Upregulated	miR-217	PRSS3/ERK/VEGF	[^Citation98]
ciRS-7 (Cdr1as)	2019	Upregulated	miR-7	EGFR/STAT3	[^Citation66]
	2021	Upregulated	miR-432-5p	E2F3	[^Citation99]
circ_0007534	2019	Upregulated	miR-625/miR-892b	-	[^Citation81]
hsa_circ_0006988 (circ-LDLRAD3)	2019	Upregulated	miR-137-3p	PTN	[^Citation100]
circFOXK2	2020	Upregulated	miR-942	ANK1/GDNF/PAX6	[^Citation73]
circHIPK3	2020	Upregulated	miR-330-5p	RASSF1	[^Citation90]
hsa_circ_001653	2020	Upregulated	miR-37	HOXC6	[^Citation101]
hsa_circ_0086375 (circNFIB1)	2020	Downregulated	miR-486-5p	PIK3R1/VEGF-C	[^Citation70]
hsa_circ_0009065 (circBFAR)	2020	Upregulated	miR-34b-5p	MET/PI3K/Akt	[^Citation45]
hsa_circ_0013912	2020	Upregulated	miR-7-5p	-	[^Citation102]
hsa_circRNA_001587 (circRNA0000979)	2020	Downregulated	miR-223	SLC4A4	[^Citation72]
hsa_circ_0066147 (circSFMBT1)	2020	Upregulated	miR-330-5p	PAK1	[^Citation103]
CircRNA_000864	2020	Downregulated	miR-361-3p	BTG2	[^Citation104]
circEIF6	2021	Upregulated	miR-557	/SLC7A11/PI3K/Akt	[^Citation105]
circNEIL3	2021	Upregulated	miR-432-5p	ADAR1	[^Citation106]
hsa_circ_0071036	2021	Upregulated	miR-489	-	[^Citation107]

Chen G , Shi Y , Zhang Y , Sun J . CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway. Onco Targets Ther . 2017;10:5783–5794. doi:10.2147/OTT.S150678 29255366

 PubMed Web of Science ®Google Scholar

Zhu P , Ge N , Liu D , et al. Preliminary investigation of the function of hsa_circ_0006215 in pancreatic cancer. Oncol Lett . 2018;16(1):603–611. doi:10.3892/ol.2018.8652 29930719

 PubMed Web of Science ®Google Scholar

Huang WJ , Wang Y , Liu S , et al. Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression. Cancer Lett . 2018;422:70–80. doi:10.1016/j.canlet.2018.02.014 29454093

 PubMed Web of Science ®Google Scholar

Ou ZL , Luo Z , Wei W , Liang S , Gao TL , Lu YB . Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: role of circ_0000977/miR-153 axis. RNA Biol . 2019;16(11):1592–1603. doi:10.1080/15476286.2019.1649585 31402756

 PubMed Web of Science ®Google Scholar

Jiang Y , Wang T , Yan L , Qu L . A novel prognostic biomarker for pancreatic ductal adenocarcinoma: hsa_circ_0001649. Gene . 2018;675:88–93. doi:10.1016/j.gene.2018.06.099 29969694

 PubMed Web of Science ®Google Scholar

Li J , Li Z , Jiang P , et al. Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis. J Exp Clin Cancer Res . 2018;37(1):177. doi:10.1186/s13046-018-0822-3 30064461

 PubMed Web of Science ®Google Scholar

An Y , Cai H , Zhang Y , et al. circZMYM2 competed endogenously with miR-335-5p to regulate JMJD2C in pancreatic cancer. Cell Physiol Biochem . 2018;51(5):2224–2236. doi:10.1159/000495868 30537731

 PubMedGoogle Scholar

Li Z , Yanfang W , Li J , et al. Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer. Cancer Lett . 2018;432:237–250. doi:10.1016/j.canlet.2018.04.035 29709702

 PubMed Web of Science ®Google Scholar

Yang J , Cong X , Ren M , et al. Circular RNA hsa_circRNA_0007334 is predicted to promote MMP7 and COL1A1 expression by functioning as a miRNA sponge in pancreatic ductal adenocarcinoma. J Oncol . 2019;2019:7630894. doi:10.1155/2019/7630894 31428151

 PubMed Web of Science ®Google Scholar

Xu Y , Yao Y , Gao P , Cui Y . Upregulated circular RNA circ_0030235 predicts unfavorable prognosis in pancreatic ductal adenocarcinoma and facilitates cell progression by sponging miR-1253 and miR-1294. Biochem Biophys Res Commun . 2019;509(1):138–142. doi:10.1016/j.bbrc.2018.12.088 30591218

 PubMed Web of Science ®Google Scholar

Chen Y , Li Z , Zhang M , et al. Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma. J Exp Clin Cancer Res . 2019;38(1):466. doi:10.1186/s13046-019-1436-0 31718694

 PubMed Web of Science ®Google Scholar

Qu S , Hao X , Song W , et al. Circular RNA circRHOT1 is upregulated and promotes cell proliferation and invasion in pancreatic cancer. Epigenomics . 2019;11(1):53–63. doi:10.2217/epi-2018-0051 30444423

 PubMed Web of Science ®Google Scholar

Ling S , He Y , Li X , et al. CircRHOT1 mediated cell proliferation, apoptosis and invasion of pancreatic cancer cells by sponging miR-125a-3p. J Cell Mol Med . 2020;24(17):9881–9889. doi:10.1111/jcmm.15572 32697386

 PubMed Web of Science ®Google Scholar

Xing C , Ye H , Wang W , et al. Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression. Artif Cells Nanomed Biotechnol . 2019;47(1):3920–3928. doi:10.1080/21691401.2019.1671856 31810373

 PubMed Web of Science ®Google Scholar

Liu L , Liu FB , Huang M , et al. Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway. Hepatobiliary Pancreat Dis Int . 2019;18(6):580–586. doi:10.1016/j.hbpd.2019.03.003 30898507

 PubMed Web of Science ®Google Scholar

Xiong X , Feng J , Yang X , et al. Circular RNA CDR1as promotes tumor progression by regulating miR-432-5p/E2F3 axis in pancreatic cancer. Cancer Cell Int . 2021;21(1):112. doi:10.1186/s12935-021-01812-3 33593338

 PubMed Web of Science ®Google Scholar

Hao L , Rong W , Bai L , et al. Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b. J Cell Biochem . 2019;120(3):3780–3789. doi:10.1002/jcb.27658 30382592

 PubMed Web of Science ®Google Scholar

Yao J , Zhang C , Chen Y , Gao S . Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis. Life Sci . 2019;239:116871. doi:10.1016/j.lfs.2019.116871 31521692

 PubMed Web of Science ®Google Scholar

Wong CH , Lou UK , Li Y , et al. CircFOXK2 promotes growth and metastasis of pancreatic ductal adenocarcinoma by complexing with RNA-binding proteins and sponging MiR-942. Cancer Res . 2020;80(11):2138–2149. doi:10.1158/0008-5472.CAN-19-3268 32217695

 PubMed Web of Science ®Google Scholar

Liu Y , Xia L , Dong L , et al. CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by sponging miR-330-5p and targets RASSF1. Cancer Manag Res . 2020;12:921–929. doi:10.2147/CMAR.S239326 32104074

 PubMed Web of Science ®Google Scholar

Shi H , Li H , Zhen T , Dong Y , Pei X , Zhang X . hsa_circ_001653 implicates in the development of pancreatic ductal adenocarcinoma by regulating microRNA-377-mediated HOXC6 axis. Mol Ther Nucleic Acids . 2020;20:252–264. doi:10.1016/j.omtn.2019.12.028 32193152

 PubMedGoogle Scholar

Kong Y , Li Y , Luo Y , et al. circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer. Mol Cancer . 2020;19(1):82. doi:10.1186/s12943-020-01205-6 32366257

 PubMed Web of Science ®Google Scholar

Guo X , Zhou Q , Su D , et al. Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis. Mol Cancer . 2020;19(1):83. doi:10.1186/s12943-020-01196-4 32375768

 PubMed Web of Science ®Google Scholar

Guo W , Zhao L , Wei G , Liu P , Zhang Y , Fu L . Blocking circ_0013912 suppressed cell growth, migration and invasion of pancreatic ductal adenocarcinoma cells in vitro and in vivo partially through sponging miR-7-5p. Cancer Manag Res . 2020;12:7291–7303. doi:10.2147/CMAR.S255808 32884344

 PubMed Web of Science ®Google Scholar

Zhang X , Tan P , Zhuang Y , Du L . Hsa_circRNA_001587 upregulates SLC4A4 expression to inhibit migration, invasion and angiogenesis of pancreatic cancer cells via binding to microRNA-223. Am J Physiol Gastrointest Liver Physiol . 2020;319(6):G703–G717. doi:10.1152/ajpgi.00118.2020 32878470

 PubMed Web of Science ®Google Scholar

Xu S , Lei SL , Liu KJ , Yi SG , Yang ZL , Yao HL . circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis. Cancer Gene Ther . 2020.

 Web of Science ®Google Scholar

Huang L , Han J , Yu H , et al. CircRNA_000864 upregulates B-cell translocation gene 2 expression and represses migration and invasion in pancreatic cancer cells by binding to miR-361-3p. Front Oncol . 2020;10:547942. doi:10.3389/fonc.2020.547942 33425718

 PubMed Web of Science ®Google Scholar

Zhang T , Li M , Lu H , Peng T . Up-regulation of circEIF6 contributes to pancreatic cancer development through targeting miR-557/SLC7A11/PI3K/AKT signaling. Cancer Manag Res . 2021;13:247–258. doi:10.2147/CMAR.S280307 33469368

 PubMed Web of Science ®Google Scholar

Shen P , Yang T , Chen Q , et al. CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing. Mol Cancer . 2021;20(1):51. doi:10.1186/s12943-021-01333-7 33750389

 PubMed Web of Science ®Google Scholar

Han X , Fang Y , Chen P , et al. Upregulated circRNA hsa_circ_0071036 promotes tumourigenesis of pancreatic cancer by sponging miR-489 and predicts unfavorable characteristics and prognosis. Cell Cycle . 2021;20(4):369–382. doi:10.1080/15384101.2021.1874684 33507122

 PubMed Web of Science ®Google Scholar