miR‑939‑3p promotes epithelial‑mesenchymal transition and may be used as a prognostic marker in hepatocellular carcinoma

Chen,Fei; Ni,Xiaoying; Chen,Lingxiu; Wang,Xiaoyan; Xu,Ji

doi:10.3892/ol.2020.11361

miR‑939‑3p promotes epithelial‑mesenchymal transition and may be used as a prognostic marker in hepatocellular carcinoma

Authors:
- Fei Chen
- Xiaoying Ni
- Lingxiu Chen
- Xiaoyan Wang
- Ji Xu
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Affiliations: Department of Digestive Center, Tiantai Branch of Zhejiang Provincial Peoples' Hospital, Taizhou, Zhejiang 317200, P.R. China, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial Peoples' Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
Published online on: January 30, 2020 https://doi.org/10.3892/ol.2020.11361
Pages: 2727-2732
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide with a high morbidity and mortality rate. An increasing number of studies have demonstrated that microRNAs (miRNAs) serve an important role in HCC. The present study investigated the role of miR‑939‑3p in HCC. It was demonstrated that miR‑939‑3p was upregulated in HCC cell lines and HCC tissues compared with normal liver cell lines and paired normal tissues, respectively. It was also found that upregulation of miR‑939‑3p expression levels in HCC tissues was associated with a less favorable prognosis. Moreover, the overexpression of miR‑939‑3p in LM3 cells enhanced the metastatic capacity of these cells and promoted epithelial‑mesenchymal transition (EMT). In contrast, miR‑939‑3p inhibition decreased the invasive capacity of HCC cells and EMT. Potential binding target of miR‑939‑3p to estrogen receptor 1 (ESR1) were predicted using TargetScan. The expression levels of miR‑939‑3p were negatively associated with ESR1 in HCC tissues based on data from The Cancer Genome Atlas. A luciferase reporter assay was used to confirm ESR1 as a direct downstream target of miR‑393‑3p. The miR‑939‑3p/ESR1 axis may be a potential novel target for the treatment of HCC.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Tan A, Yeh SH, Liu CJ, Cheung C and Chen PJ: Viral hepatocarcinogenesis: From infection to cancer. Liver Int. 28:175–188. 2008. View Article : Google Scholar : PubMed/NCBI
3	Ren FH, Yang H, He RQ, Lu JN, Lin XG, Liang HW, Dang YW, Feng ZB, Chen G and Luo DZ: Analysis of microarrays of miR-34a and its identification of prospective target gene signature in hepatocellular carcinoma. BMC Cancer. 18:122018. View Article : Google Scholar : PubMed/NCBI
4	Brondfield MN, Dodge JL, Hirose R, Heimbach J, Yao FY and Mehta N: Hepatocellular carcinoma (HCC) patients listed in short wait regions remain advantaged for liver transplant (LT) following 2015 HCC policy change. Liver Transpl. Dec 13–2019.doi: 10.1002/lt.25701 (Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
5	Bakheet AMH, Zhao C, Chen JN, Zhang JY, Huang JT, Du Y, Gong LP, Bi YH and Shao CK: Improving pathological early diagnosis and differential biomarker value for hepatocellular carcinoma via RNAscope technology. Hepatol Int. Dec 12–2019.doi: 10.1007/s12072-019-10006-z (Epub ahead of print). PubMed/NCBI
6	Hu J, Wang E, Liu L, Wang Q, Xia D, Bai W, Tie J, Li X, Yuan J, Yang S, et al: Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells. Invest New Drugs. Dec 13–2019.doi: 10.1007/s10637-019-00885-2 (Epub ahead of print). View Article : Google Scholar
7	Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH and Cuppen E: Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 120:21–24. 2005. View Article : Google Scholar : PubMed/NCBI
8	Rana TM: Illuminating the silence: Understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol. 8:23–36. 2007. View Article : Google Scholar : PubMed/NCBI
9	Loosen SH, Schueller F, Trautwein C, Roy S and Roderburg C: Role of circulating microRNAs in liver diseases. World J Hepatol. 9:586–594. 2017. View Article : Google Scholar : PubMed/NCBI
10	Huang X, Wang L, Liu W and Li F: MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2. Oncol Lett. 17:3425–3431. 2019.PubMed/NCBI
11	Ni JS, Zheng H, Huang ZP, Hong YG, Ou YL, Tao YP, Wang MC, Wang ZG, Yang Y and Zhou WP: MicroRNA-197-3p acts as a prognostic marker and inhibits cell invasion in hepatocellular carcinoma. Oncol Lett. 17:2317–2327. 2019.PubMed/NCBI
12	Tang Z, Fang Y and Du R: MicroRNA-107 induces cell cycle arrests by directly targeting cyclin E1 in ovarian cancer. Biochem Biophys Res Commun. 512:331–337. 2019. View Article : Google Scholar : PubMed/NCBI
13	Wang J, Chu Y and Xu M, Zhang X, Zhou Y and Xu M: miR-21 promotes cell migration and invasion of hepatocellular carcinoma by targeting KLF5. Oncol Lett. 17:2221–2227. 2019.PubMed/NCBI
14	Chen A, Liu S, Lu X, Wei L and Chen Y: Inhibition of microRNA939 suppresses the development of human nonsmall cell lung cancer via the upregulation of tissue inhibitor of metalloproteinases 2. Mol Med Rep. 18:4831–4838. 2018.PubMed/NCBI
15	Bjornstrom L and Sjoberg M: Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes. Mol Endocrinol. 19:833–842. 2005. View Article : Google Scholar : PubMed/NCBI
16	Yang J, AlTahan A, Jones DT, Buffa FM, Bridges E, Interiano RB, Qu C, Vogt N, Li JL, Baban D, et al: Estrogen receptor-alpha directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. Proc Natl Acad Sci USA. 112:15172–15177. 2015. View Article : Google Scholar : PubMed/NCBI
17	Andruska ND, Zheng X, Yang X, Mao C, Cherian MM, Mahapatra L, Helferich WG and Shapiro DJ: Estrogen receptor α inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression. Proc Natl Acad Sci USA. 112:4737–4742. 2015. View Article : Google Scholar : PubMed/NCBI
18	Hishida M, Nomoto S, Inokawa Y, Hayashi M, Kanda M, Okamura Y, Nishikawa Y, Tanaka C, Kobayashi D, Yamada S, et al: Estrogen receptor 1 gene as a tumor suppressor gene in hepatocellular carcinoma detected by triple-combination array analysis. Int J Oncol. 43:88–94. 2013. View Article : Google Scholar : PubMed/NCBI
19	Tu CC, Kumar VB, Day CH, Kuo WW, Yeh SP, Chen RJ, Liao CR, Chen HY, Tsai FJ, Wu WJ and Huang CY: Estrogen receptor alpha (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins. J Mol Endocrinol. 51:203–212. 2013. View Article : Google Scholar : PubMed/NCBI
20	Nagy Á, Lánczky A, Menyhárt O and Győrffy B: Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 8:92272018. View Article : Google Scholar : PubMed/NCBI
21	Wan J, Liu H, Yang L, Ma L, Liu J and Ming L: JMJD6 promotes hepatocellular carcinoma carcinogenesis by targeting CDK4. Int J Cancer. 144:2489–2500. 2019. View Article : Google Scholar : PubMed/NCBI
22	Hu D, Hu Y, Xu W, Yu H, Yang N, Ni S and Fu R: miR203 inhibits the expression of collagenrelated genes and the proliferation of hepatic stellate cells through a SMAD3dependent mechanism. Mol Med Rep. 16:1248–1254. 2017. View Article : Google Scholar : PubMed/NCBI
23	Wan X, Cheng C, Shao Q, Lin Z, Lu S and Chen Y: CD24 promotes HCC progression via triggering Notch-related EMT and modulation of tumor microenvironment. Tumour Biol. 37:6073–6084. 2016. View Article : Google Scholar : PubMed/NCBI
24	Hu Y, Yang C, Yang S, Cheng F, Rao J and Wang X: miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB. Cell Death Dis. 9:9542018. View Article : Google Scholar : PubMed/NCBI
25	Zhang XP, Jiang YB, Zhong CQ, Ma N, Zhang EB, Zhang F, Li JJ, Deng YZ, Wang K, Xie D and Cheng SQ: PRMT1 promoted HCC growth and metastasis in vitro and in vivo via activating the STAT3 signalling pathway. Cell Physiol Biochem. 47:1643–1654. 2018. View Article : Google Scholar : PubMed/NCBI
26	Yu H, Shen H, Zhang Y, Zhong F, Liu Y, Qin L and Yang P: CAV1 promotes HCC cell progression and metastasis through Wnt/β-catenin pathway. PLoS One. 9:e1064512014. View Article : Google Scholar : PubMed/NCBI
27	Li Y, Chen L, Chan TH, Liu M, Kong KL, Qiu JL, Li Y, Yuan YF and Guan XY: SPOCK1 is regulated by CHD1L and blocks apoptosis and promotes HCC cell invasiveness and metastasis in mice. Gastroenterology. 144:179–191 e174. 2013. View Article : Google Scholar : PubMed/NCBI
28	Feng L, Jing L, Han J, Wang G and Liu Y, Zhang X, Wang Y, Wang F, Ma H and Liu Y: MicroRNA 486–3p directly targets BIK and regulates apoptosis and invasion in colorectal cancer cells. Onco Targets Ther. 11:8791–8801. 2018. View Article : Google Scholar : PubMed/NCBI
29	Liang M, Shi B, Liu J, He L, Yi G, Zhou L, Yu G and Zhou X: Downregulation of miR203 induces overexpression of PIK3CA and predicts poor prognosis of gastric cancer patients. Drug Des Devel Ther. 9:3607–3616. 2015.PubMed/NCBI
30	Wang ZY, Zhu Z, Wang HF, Qin B, Liu J, Yao XH, Li WC and Chen KS: Downregulation of circDYNC1H1 exhibits inhibitor effect on cell proliferation and migration in hepatocellular carcinoma through miR-140-5p. J Cell Physiol. 234:17775–17785. 2019. View Article : Google Scholar : PubMed/NCBI
31	Yu W, Deng W, Zhao Q, Zhuang H, Zhang C and Jian Z: miR-501 acts as an independent prognostic factor that promotes the epithelial-mesenchymal transition through targeting JDP2 in hepatocellular carcinoma. Hum Cell. 32:343–351. 2019. View Article : Google Scholar : PubMed/NCBI