Downregulation of miR‑552 in hepatocellular carcinoma inhibits cell migration and invasion, and promotes cell apoptosis via RUNX3

Ma,Ying; Ma,Ming; Ma,Ling; Zhang,Fengbo; Liu,Yumei; Ma,Xiumin

doi:10.3892/etm.2019.8061

Downregulation of miR‑552 in hepatocellular carcinoma inhibits cell migration and invasion, and promotes cell apoptosis via RUNX3

Authors:
- Ying Ma
- Ming Ma
- Ling Ma
- Fengbo Zhang
- Yumei Liu
- Xiumin Ma
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Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang 830054, P.R. China, Department of Hepatobiliary Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumchi, Xinjiang 830001, P.R. China, Department of Pharmacy, Thoracic Hospital of Xinjiang Uygur Autonomous Region, Urumchi, Xinjiang 830049, P.R. China
Published online on: September 27, 2019 https://doi.org/10.3892/etm.2019.8061
Pages: 3829-3836
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Research conducted previously has indicated that microRNAs (miRs) have potential effects on the pathogenesis of hepatocellular carcinoma (HCC). The biological functions of miR‑552 have been well documented in colon cancer; however, the role of miR‑552 in HCC remains unclear. The present study evaluated the effects of miR‑552 in HCC physiology, using HCC cell lines as model. An miR‑552 inhibitor was transfected into HCC cell lines to knock down the expression of miR‑552. Reverse transcription‑quantitative PCR and western blot analysis were used to detect the expression of miR‑552 and Runt‑related transcription factor 3 (RUNX3), respectively. MTT assay was used to analyze cell viability, whilst Transwell and wound‑healing assay were used to investigate cell migration. Flow cytometry was performed to measure cell apoptosis. The direct association between RUNX3 and miR‑552 was evaluated using dual luciferase reporter assay. The expression of miR‑552 was significantly elevated in HCC tumor tissues compared with the adjacent healthy samples. Additionally, transfection with the miR‑552 inhibitor decreased cell viability and migration. miR‑552 knockdown also increased HCC cell apoptosis in vitro. In conclusion, these results suggest that miR‑552 has an oncogenic function in HCC and is a potential biomarker for detecting HCC.

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1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
3	Forner A, Hessheimer AJ, Isabel Real M and Bruix J: Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 60:89–98. 2006. View Article : Google Scholar : PubMed/NCBI
4	Guglielmi A, Ruzzenente A, Conci S, Valdegamberi A, Vitali M, Bertuzzo F, De Angelis M, Mantovani G and Iacono C: Hepatocellular carcinoma: Surgical perspectives beyond the barcelona clinic liver cancer recommendations. World J Gastroenterol. 20:7525–7533. 2014. View Article : Google Scholar : PubMed/NCBI
5	Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, et al: Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:15524–15529. 2002. View Article : Google Scholar : PubMed/NCBI
6	Fiorino S, Bacchi-Reggiani ML, Visani M, Acquaviva G, Fornelli A, Masetti M, Tura A, Grizzi F, Zanello M, Mastrangelo L, et al: MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma. World J Gastroenterol. 22:3907–3936. 2016. View Article : Google Scholar : PubMed/NCBI
7	Hayes CN and Chayama K: MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci. 17:2802016. View Article : Google Scholar : PubMed/NCBI
8	Hua S, Liu C, Liu L and Wu D: miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA. Biochem Biophys Res Commun. 496:947–954. 2018. View Article : Google Scholar : PubMed/NCBI
9	Zhang W, Qian S, Yang G, Zhu L, Zhou B, Wang J, Liu R, Yan Z and Qu X: MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma. Gene. 659:22–28. 2018. View Article : Google Scholar : PubMed/NCBI
10	Cao J, Yan XR, Liu T, Han XB, Yu JJ, Liu SH and Wang LB: MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer. Oncol Lett. 14:3795–3802. 2017. View Article : Google Scholar : PubMed/NCBI
11	Wang J, Li H, Wang Y, Wang L, Yan X, Zhang D, Ma X, Du Y, Liu X and Yang Y: MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28. Oncotarget. 7:70194–70210. 2016.PubMed/NCBI
12	Gou Y, Zhai F, Zhang L and Cui L: RUNX3 regulates hepatocellular carcinoma cell metastasis via targeting miR-186/E-cadherin/EMT pathway. Oncotarget. 8:61475–61486. 2017. View Article : Google Scholar : PubMed/NCBI
13	Chen Y, Wang X, Cheng J, Wang Z, Jiang T, Hou N, Liu N, Song T and Huang C: MicroRNA-20a-5p targets RUNX3 to regulate proliferation and migration of human hepatocellular cancer cells. Oncol Rep. 36:3379–3386. 2016. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Schmidt VM, Isachenko E, Rappl G, Rahimi G, Hanstein B, Morgenstern B, Mallmann P and Isachenko V: Construction of human artificial ovary from cryopreserved ovarian tissue: Appearance of apoptosis and necrosis after enzymatic isolation of follicles. Cryobiology. 84:10–14. 2018. View Article : Google Scholar : PubMed/NCBI
16	Hong Z, Cao X, Li N, Zhang Y, Lan L, Zhou Y, Pan X, Shen L, Yin Z and Luo L: Luteolin is effective in the non-small cell lung cancer model with L858R/T790M EGF receptor mutation and erlotinib resistance. Br J Pharmacol. 171:2842–2853. 2014. View Article : Google Scholar : PubMed/NCBI
17	Chen Z, Zuo X, Pu L, Zhang Y, Han G, Zhang L, Wu J and Wang X: circLARP4 induces cellular senescence through regulating miR-761/RUNX3/p53/p21 signaling in hepatocellular carcinoma. Cancer Sci. 110:568–581. 2019. View Article : Google Scholar : PubMed/NCBI
18	Kondili LA, Lala A, Gunson B, Hubscher S, Olliff S, Elias E, Bramhall S and Mutimer D: Primary hepatocellular cancer in the explanted liver: Outcome of transplantation and risk factors for HCC recurrence. Eur J Surg Oncol. 33:868–873. 2007. View Article : Google Scholar : PubMed/NCBI
19	Duan J, Hu C, Qiu Q, Zhang J, Meng H, Wang K, Dong H, Wei H and Yin Y: Characterization of microvessels and parenchyma in in-line phase contrast imaging CT: Healthy liver, cirrhosis and hepatocellular carcinoma. Quant Imaging Med Surg. 9:1037–1046. 2019. View Article : Google Scholar : PubMed/NCBI
20	Jin K, Li T, Sanchez-Duffhues G, Zhou F and Zhang L: Involvement of inflammation and its related microRNAs in hepatocellular carcinoma. Oncotarget. 8:22145–22165. 2017.PubMed/NCBI
21	Chu R, Mo G, Duan Z, Huang M, Chang J, Li X and Liu P: miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression. Cell Commun Signal. 12:452014. View Article : Google Scholar : PubMed/NCBI
22	Callegari E, Gramantieri L, Domenicali M, D'Abundo L, Sabbioni S and Negrini M: MicroRNAs in liver cancer: A model for investigating pathogenesis and novel therapeutic approaches. Cell Death Differ. 22:46–57. 2014. View Article : Google Scholar : PubMed/NCBI
23	Kim J, Lim NJ, Jang SG, Kim HK and Lee GK: miR-592 and miR-552 can distinguish between primary lung adenocarcinoma and colorectal cancer metastases in the lung. Anticancer Res. 34:2297–2302. 2014.PubMed/NCBI
24	Leivonen SK, Sahlberg KK, Mäkelä R, Due EU, Kallioniemi O, Børresen-Dale AL and Perälä M: High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Mol Oncol. 8:93–104. 2014. View Article : Google Scholar : PubMed/NCBI
25	Juraver-Geslin HA and Durand BC: Early development of the neural plate: New roles for apoptosis and for one of its main effectors caspase-3. Genesis. 53:203–224. 2015. View Article : Google Scholar : PubMed/NCBI
26	Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C and Kroemer G: Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13:1423–1433. 2006. View Article : Google Scholar : PubMed/NCBI
27	Guo J, Zhang K, Ji Y, Jiang X and Zuo S: Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. J Huazhong Univ Sci Technolog Med Sci. 28:281–283. 2008. View Article : Google Scholar : PubMed/NCBI
28	Zhang C, Li J, Huang T, Duan S, Dai D, Jiang D, Sui X, Li D, Chen Y, Ding F, et al: Meta-analysis of DNA methylation biomarkers in hepatocellular carcinoma. Oncotarget. 7:81255–81267. 2016. View Article : Google Scholar : PubMed/NCBI