miR-154 targeting ZEB2 in hepatocellular carcinoma functions as a potential tumor suppressor Retraction in /10.3892/or.2021.8113

Pang,Xiaoli; Huang,Kexin; Zhang,Qianqian; Zhang,Yujiao; Niu,Junqi

doi:10.3892/or.2015.4321

miR-154 targeting ZEB2 in hepatocellular carcinoma functions as a potential tumor suppressor

Retraction in: /10.3892/or.2021.8113

Authors:
- Xiaoli Pang
- Kexin Huang
- Qianqian Zhang
- Yujiao Zhang
- Junqi Niu
View Affiliations

Affiliations: Department of Pediatric Gastroenterology, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, The Experiment Center, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hepatology, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: October 1, 2015 https://doi.org/10.3892/or.2015.4321
Pages: 3272-3279

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNA-154 (miR-154) has been identified as a tumor suppressor in several types of human cancers; however, its clinical significance and function in human hepatocellular carcinoma (HCC) remain unclear. The aim of the present study was to analyze the clinical significance and cellular function of miR-154 in HCC patients. The data showed that miR-154 expression was consistently lower in HCC tissues and cell lines compared to that in matched tumor-adjacent tissues and a normal hepatic cell line, and its expression was negatively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Restoration of miR-154 expression in HepG2 cells inhibited cell proliferation, migration and invasion, and induced apoptosis and cell arrest at the G1 phase in vitro, as well as suppressed tumor growth in a nude mouse model. Using a luciferase assay, we identified that miR-154 was able to target the 3'-untranslated region (3'UTR) of ZEB2 mRNA. Then, we revealed that miR-154 was able to reduce ZEB2 expression at the levels of mRNA and protein using qRT-PCR and western blot analysis. Notably, restoration of expression of ZEB2 weakened miR-154-mediated suppression of tumor progression. In conclusion, these results indicate that miR-154 functions as a tumor suppressor in HCC by suppressing ZEB2, suggesting that miR-154 may serve as a potential target for HCC.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, Wang J, Chen CS, Chen J, Wildman RP, et al: Major causes of death among men and women in China. N Engl J Med. 353:1124–1134. 2005. View Article : Google Scholar : PubMed/NCBI
3	Livraghi T, Makisalo H and Line PD: Treatment options in hepatocellular carcinoma today. Scand J Surg. 100:22–29. 2011.PubMed/NCBI
4	Thorgeirsson SS and Grisham JW: Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 31:339–346. 2002. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Malan-Müller S, Hemmings SM and Seedat S: Big effects of small RNAs: A review of microRNAs in anxiety. Mol Neurobiol. 47:726–739. 2013. View Article : Google Scholar :
7	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
8	Guo H, Ingolia NT, Weissman JS and Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 466:835–840. 2010. View Article : Google Scholar : PubMed/NCBI
9	McManus MT: MicroRNAs and cancer. Semin Cancer Biol. 13:253–258. 2003. View Article : Google Scholar : PubMed/NCBI
10	Farazi TA, Spitzer JI, Morozov P and Tuschl T: miRNAs in human cancer. J Pathol. 223:102–115. 2011. View Article : Google Scholar :
11	Garzon R and Marcucci G: Potential of microRNAs for cancer diagnostics, prognostication and therapy. Curr Opin Oncol. 24:655–659. 2012. View Article : Google Scholar : PubMed/NCBI
12	Li G, Shen Q, Li C, Li D, Chen J and He M: Identification of circulating microRNAs as novel potential biomarkers for hepatocellular carcinoma detection: A systematic review and meta-analysis. Clin Transl Oncol. 7:684–693. 2015. View Article : Google Scholar
13	Saito Y, Suzuki H, Matsuura M, Sato A, Kasai Y, Yamada K, Saito H and Hibi T: MicroRNAs in hepatobiliary and pancreatic cancers. Front Genet. 2:662011. View Article : Google Scholar
14	Lin SP, Youngson N, Takada S, Seitz H, Reik W, Paulsen M, Cavaille J and Ferguson-Smith AC: Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nat Genet. 35:97–102. 2003. View Article : Google Scholar : PubMed/NCBI
15	Wang W, Peng B, Wang D, Ma X, Jiang D, Zhao J and Yu L: Human tumor microRNA signatures derived from large-scale oligonucleotide microarray datasets. Int J Cancer. 129:1624–1634. 2011. View Article : Google Scholar
16	Miranda PJ, Vimalraj S and Selvamurugan N: A feedback expression of microRNA-590 and activating transcription factor-3 in human breast cancer cells. Int J Biol Macromol. 72:145–150. 2015. View Article : Google Scholar
17	Lin X, Yang Z, Zhang P and Shao G: miR-154 suppresses non-small cell lung cancer growth in vitro and in vivo. Oncol Rep. 33:3053–3060. 2015.PubMed/NCBI
18	Xin C, Zhang H and Liu Z: miR-154 suppresses colorectal cancer cell growth and motility by targeting TLR2. Mol Cell Biochem. 387:271–277. 2014. View Article : Google Scholar
19	Mian C, Pennelli G, Fassan M, Balistreri M, Barollo S, Cavedon E, Galuppini F, Pizzi M, Vianello F, Pelizzo MR, et al: MicroRNA profiles in familial and sporadic medullary thyroid carcinoma: Preliminary relationships with RET status and outcome. Thyroid. 22:890–896. 2012. View Article : Google Scholar : PubMed/NCBI
20	Yang Z, Sun B, Li Y, Zhao X, Zhao X, Gu Q, An J, Dong X, Liu F and Wang Y: ZEB2 promotes vasculogenic mimicry by TGF-β1 induced epithelial-to-mesenchymal transition in hepatocellular carcinoma. Exp Mol Pathol. 98:352–359. 2015. View Article : Google Scholar : PubMed/NCBI
21	Liu K, Liu S, Zhang W, Ji B, Wang Y and Liu Y: miR-222 regulates sorafenib resistance and enhance tumorigenicity in hepatocellular carcinoma. Int J Oncol. 45:1537–1546. 2014.PubMed/NCBI
22	Liu K, Liu S, Zhang W, Jia B, Tan L, Jin Z and Liu Y: miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN. Oncol Rep. 34:1003–1010. 2015.PubMed/NCBI
23	Chai ZT, Zhu XD, Ao JY, Wang WQ, Gao DM, Kong J, Zhang N, Zhang YY, Ye BG, Ma DN, et al: microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol. 8:562015. View Article : Google Scholar : PubMed/NCBI
24	Jiang G, Cui Y, Yu X, Wu Z, Ding G and Cao L: miR-211 suppresses hepatocellular carcinoma by downregulating SATB2. Oncotarget. 6:9457–9466. 2015. View Article : Google Scholar : PubMed/NCBI
25	Verschueren K, Remacle JE, Collart C, Kraft H, Baker BS, Tylzanowski P, Nelles L, Wuytens G, Su MT, Bodmer R, et al: SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5′-CACCT sequences in candidate target genes. J Biol Chem. 274:20489–20498. 1999. View Article : Google Scholar : PubMed/NCBI
26	Cai MY, Luo RZ, Chen JW, Pei XQ, Lu JB, Hou JH and Yun JP: Overexpression of ZEB2 in peritumoral liver tissue correlates with favorable survival after curative resection of hepatocellular carcinoma. PLoS One. 7:e328382012. View Article : Google Scholar : PubMed/NCBI
27	Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D and van Roy F: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 7:1267–1278. 2001. View Article : Google Scholar : PubMed/NCBI
28	Vandewalle C, Comijn J, De Craene B, Vermassen P, Bruyneel E, Andersen H, Tulchinsky E, Van Roy F and Berx G: SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Res. 33:6566–6578. 2005. View Article : Google Scholar : PubMed/NCBI
29	Qiu G, Lin Y, Zhang H and Wu D: miR-139-5p inhibits epithelial-mesenchymal transition, migration and invasion of hepatocellular carcinoma cells by targeting ZEB1 and ZEB2. Biochem Biophys Res Commun. 463:315–321. 2015. View Article : Google Scholar : PubMed/NCBI
30	Yang X, Wang J, Qu S, Zhang H, Ruan B, Gao Y, Ma B, Wang X, Wu N, Li X, et al: MicroRNA-200a suppresses metastatic potential of side population cells in human hepatocellular carcinoma by decreasing ZEB2. Oncotarget. 6:7918–7929. 2015. View Article : Google Scholar : PubMed/NCBI
31	Wu SM, Ai HW, Zhang DY, Han XQ, Pan Q, Luo FL and Zhang XL: miR-141 targets ZEB2 to suppress HCC progression. Tumour Biol. 35:9993–9997. 2014. View Article : Google Scholar : PubMed/NCBI