Abstract
Hepatocellular carcinoma (HCC) remains a lethal cancer type for both males and females. MicroRNAs (miRNAs) contribute to the initiation, development and metastasis of cancer. Although several miRNAs have been identified as drivers or suppressors of HCC, the molecular mechanisms of many miRNAs have not been investigated. Currently, we discovered that miR-4270-5p was a significantly downregulated miRNA in HCC. We revealed that miR-4270-5p overexpression inhibited cell proliferation and invasion of HCC cells. The data manifested that miR-4270-5p directly targeted SATB2, a key regulator of epithelial mesenchymal transition (EMT), in HCC cells and reversed the EMT process. The rescue experiments suggested that SATB2 overexpression reversed the biological function of miR-4270-5p in HCC cells. Clinical data indicated that SATB2 expression was negatively correlated with miR-4270-5p levels in HCC patients. Our findings provided potential targets for prognosis and treatment of patients with HCC.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study are included in this published article.
References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
Zahid KR, Han S, Zhou F, Raza U. Novel tumor suppressor SPRYD4 inhibits tumor progression in hepatocellular carcinoma by inducing apoptotic cell death. Cell Oncol (Dordr). 2019;42(1):55–66.
Gomes MA, Priolli DG, Tralhao JG, Botelho MF. Hepatocellular carcinoma: epidemiology, biology, diagnosis, and therapies. Rev Assoc Med Bras (1992). 2013;59(5):514–24.
Campsen J, Zimmerman M, Trotter J, et al. Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues. Liver Transpl. 2013;19(9):1020–9.
Kondo M, Moriishi K, Wada H, et al. Upregulation of nuclear PA28gamma expression in cirrhosis and hepatocellular carcinoma. Exp Ther Med. 2012;3(3):379–85.
Zhang N, Chen X. A positive feedback loop involving the LINC00346/beta-catenin/MYC axis promotes hepatocellular carcinoma development. Cell Oncol (Dordr). 2020;43(1):137–53.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.
Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25(17):2537–45.
Huang DH, Wang GY, Zhang JW, Li Y, Zeng XC, Jiang N. MiR-501-5p regulates CYLD expression and promotes cell proliferation in human hepatocellular carcinoma. Jpn J Clin Oncol. 2015;45(8):738–44.
Jiang C, Yu M, Xie X, et al. miR-217 targeting DKK1 promotes cancer stem cell properties via activation of the Wnt signaling pathway in hepatocellular carcinoma. Oncol Rep. 2017;38(4):2351–9.
Kim J, Jiang J, Badawi M, Schmittgen TD. miR-221 regulates CD44 in hepatocellular carcinoma through the PI3K-AKT-mTOR pathway. Biochem Biophys Res Commun. 2017;487(3):709–15.
Hua S, Liu C, Liu L, Wu D. miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA. Biochem Biophys Res Commun. 2018;496(3):947–54.
Wei R, Huang GL, Zhang MY, et al. Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma. Clin Cancer Res. 2013;19(17):4780–91.
Aprelikova O, Yu X, Palla J, et al. The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle. 2010;9(21):4387–98.
Luo LJ, Yang F, Ding JJ, et al. MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer. Gene. 2016;594(1):47–58.
Patani N, Jiang W, Mansel R, Newbold R, Mokbel K. The mRNA expression of SATB1 and SATB2 in human breast cancer. Cancer Cell Int. 2009;9:18.
Gu J, Wang G, Liu H, Xiong C. SATB2 targeted by methylated miR-34c-5p suppresses proliferation and metastasis attenuating the epithelial-mesenchymal transition in colorectal cancer. Cell Prolif. 2018;51(4):e12455.
Gan X, Jiang J, Wu G, Chen D, Liao D, Li M. SATB2 induces stem-like properties and promotes epithelial–mesenchymal transition in hepatocellular carcinoma. Int J Clin Exp Pathol. 2017;10(12):11932–40.
Abdel-Rahman O. Assessment of the discriminating value of the 8th AJCC stage grouping for hepatocellular carcinoma. HPB (Oxford). 2018;20(1):41–8.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(− Delta Delta C(T)) method. Methods. 2001;25(4):402–8.
Zhu HR, Huang RZ, Yu XN, et al. Microarray expression profiling of microRNAs reveals potential biomarkers for hepatocellular carcinoma. Tohoku J Exp Med. 2018;245(2):89–988.
Karaosmanoglu O, Banerjee S, Sivas H. Identification of biomarkers associated with partial epithelial to mesenchymal transition in the secretome of slug over-expressing hepatocellular carcinoma cells. Cell Oncol (Dordr). 2018;41(4):439–53.
Sun G, Ding X, Bi N, et al. Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma. PLoS Genet. 2019;15(2):e1007888.
Tsai WC, Hsu PW, Lai TC, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571–82.
Zou A, Liu X, Mai Z, et al. LINC00472 acts as a tumor suppressor in NSCLC through KLLN-mediated p53-signaling pathway via microRNA-149-3p and microRNA-4270. Mol Ther Nucleic Acids. 2019;17:563–77.
Hu X, Zhai Y, Kong P, et al. FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer. Cancer Lett. 2017;397:83–93.
Jaca A, Govender P, Locketz M, Naidoo R. The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer. J Clin Pathol. 2017;70(4):331–56.
Zhu H, Zhou X, Ma C, et al. Low expression of miR-448 induces EMT and promotes invasion by regulating ROCK2 in hepatocellular carcinoma. Cell Physiol Biochem. 2015;36(2):487–98.
Ma YN, Zhang HY, Fei LR, et al. SATB2 suppresses non-small cell lung cancer invasiveness by G9a. Clin Exp Med. 2018;18(1):37–44.
Chen QY, Des Marais T, Costa M. Deregulation of SATB2 in carcinogenesis with emphasis on miRNA-mediated control. Carcinogenesis. 2019;40(3):393–402.
Wei J, Shi Y, Zheng L, et al. miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2. J Cell Biol. 2012;197(4):509–21.
Jiang G, Cui Y, Yu X, Wu Z, Ding G, Cao L. miR-211 suppresses hepatocellular carcinoma by downregulating SATB2. Oncotarget. 2015;6(11):9457–66.
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All the authors declare that they have no competing interests of any type in the current study.
Ethical standards
The study was performed in accordance with the Declaration of Helsinki and obtained the approval from the Ethics Committee of the China-Japan Union Hospital of Jilin University.
Informed consent
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wang, Y., Li, Cf., Sun, Lb. et al. microRNA-4270-5p inhibits cancer cell proliferation and metastasis in hepatocellular carcinoma by targeting SATB2. Human Cell 33, 1155–1164 (2020). https://doi.org/10.1007/s13577-020-00384-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13577-020-00384-0