MicroRNA‑744 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12

  • Authors:
    • Wei Zhang
    • Kai Liu
    • Songyang Liu
    • Bai Ji
    • Yahui Liu
  • View Affiliations

  • Published online on: October 8, 2018     https://doi.org/10.3892/or.2018.6774
  • Pages: 3585-3592
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Abstract

MicroRNA‑744 (miR‑744) reportedly plays an oncogenic or tumor‑suppressive role in different human malignancies. Although a previous study demonstrated that miR‑744 significantly inhibits hepatocellular carcinoma (HCC) proliferation in vitro, the role of miR‑744 in the migration and invasion of HCC cells remains largely unknown. The present study investigated the significance of miR‑744 in HCC tissues and cell lines and evaluated its role and underlying mechanism of action in HCC cells. miR‑744 expression was detected in HCC tissues and cell lines by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The effect of miR‑744 on cell proliferation, migration and invasion was determined using Cell Counting Kit‑8, wound‑healing and Matrigel invasion assays, respectively. Targeting gene of miR‑744 in HCC cells was determined by luciferase reporter assay, RT‑qPCR and western blotting. It was revealed that miR‑744 was poorly expressed in HCC tissues compared with adjacent normal tissues (P<0.05), and that decreased miR‑744 levels were significantly associated with the tumor node metastasis stage and lymph node metastasis. Additionally, restoration of miR‑744 in HCC cells significantly suppressed their proliferation, migration, and invasion. Furthermore, sex determining region Y‑box 12 (SOX12) was identified as a functional target of miR‑744 in HCC cells, and its expression was demonstrated to be upregulated in HCC tissues and inversely correlated with the expression of miR‑744. Notably, overexpression of SOX12 antagonized the suppressive effect of miR‑744 on HCC cell migration and invasion. These findings suggested that miR‑744 inhibited migration and invasion by targeting SOX12, and that it may represent a therapeutic target for the treatment of metastatic HCC.

References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Venook AP, Papandreou C, Furuse J and de Guevara LL: The incidence and epidemiology of hepatocellular carcinoma: A global and regional perspective. Oncologist. 15 Suppl 4:S5–S13. 2010. View Article : Google Scholar

3 

Lau WY and Lai EC: Hepatocellular carcinoma: Current management and recent advances. Hepatobiliary Pancreat Dis Int. 7:237–257. 2008.PubMed/NCBI

4 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Pillai RS: MicroRNA function: Multiple mechanisms for a tiny RNA? RNA. 11:1753–1761. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Hayes J, Peruzzi PP and Lawler S: MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med. 20:460–469. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Mao B and Wang G: MicroRNAs involved with hepatocellular carcinoma (Review). Oncol Rep. 34:2811–2820. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Giordano S and Columbano A: MicroRNAs: New tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 57:840–847. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Yu Q, Zhang F, Du Z and Xiang Y: Up-regulation of serum miR-744 predicts poor prognosis in patients with nasopharyngeal carcinoma. Int J Clin Exp Med. 8:13296–13302. 2015.PubMed/NCBI

10 

Zhou W, Li Y, Gou S, Xiong J, Wu H, Wang C, Yan H and Liu T: MiR-744 increases tumorigenicity of pancreatic cancer by activating Wnt/beta-catenin pathway. Oncotarget. 6:37557–37569. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Fang Y, Zhu X, Wang J, Li N, Li D, Sakib N, Sha Z and Song W: MiR-744 functions as a proto-oncogene in nasopharyngeal carcinoma progression and metastasis via transcriptional control of ARHGAP5. Oncotarget. 6:13164–13175. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Vislovukh A, Kratassiouk G, Porto E, Gralievska N, Beldiman C, Pinna G, El'skaya A, Harel-Bellan A, Negrutskii B and Groisman I: Proto-oncogenic isoform A2 of eukaryotic translation elongation factor eEF1 is a target of miR-663 and miR-744. Br J Cancer. 108:2304–2311. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Guan H, Liu C, Fang F, Huang Y, Tao T, Ling Z, You Z, Han X, Chen S, Xu B and Chen M: MicroRNA-744 promotes prostate cancer progression through aberrantly activating Wnt/beta-catenin signaling. Oncotarget. 8:14693–14707. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Chen XF and Liu Y: MicroRNA-744 inhibited cervical cancer growth and progression through apoptosis induction by regulating Bcl-2. Biomed Pharmacother. 81:379–387. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Tan YL, Bai ZG, Zou WL, Ma XM, Wang TT, Guo W, Liu J, Li JS, Jie Yin, Zang YJ, et al: miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 39:359–365. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Lin F, Ding R, Zheng S, Xing D, Hong W, Zhou Z and Shen J: Decrease expression of microRNA-744 promotes cell proliferation by targeting c-Myc in human hepatocellular carcinoma. Cancer Cell Int. 14:582014. View Article : Google Scholar : PubMed/NCBI

17 

Edge SB and Compton CC: The American joint committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Ding H, Quan H, Yan W and Han J: Silencing of SOX12 by shRNA suppresses migration, invasion and proliferation of breast cancer cells. Biosci Rep. 36:e003892016. View Article : Google Scholar :

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Liu Y, Zhang W, Liu S, Liu K, Ji B and Wang Y: miR-365 targets ADAM10 and suppresses the cell growth and metastasis of hepatocellular carcinoma. Oncol Rep. 37:1857–1864. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Huang JT, Liu SM, Ma H, Yang Y, Zhang X, Sun H, Zhang X, Xu J and Wang J: Systematic review and meta-analysis: Circulating miRNAs for diagnosis of hepatocellular carcinoma. J Cell Physiol. 231:328–335. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Khare S, Zhang Q and Ibdah JA: Epigenetics of hepatocellular carcinoma: Role of microRNA. World J Gastroenterol. 19:5439–5445. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Nurul-Syakima AM, Yoke-Kqueen C, Sabariah AR, Shiran MS, Singh A and Learn-Han L: Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers. Int J Mol Med. 28:327–336. 2011.PubMed/NCBI

24 

Sha Z, Zhu X, Li N, Li Y and Li D: Proto-oncogenic miR-744 is upregulated by transcription factor c-Jun via a promoter activation mechanism. Oncotarget. 7:64977–64986. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Hoser M, Potzner MR, Koch JM, Bosl MR, Wegner M and Sock E: Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors. Mol Cell Biol. 28:4675–4687. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Huang W, Chen Z, Shang X, Tian D, Wang D, Wu K, Fan D and Xia L: Sox12, a direct target of FoxQ1, promotes hepatocellular carcinoma metastasis through up-regulating Twist1 and FGFBP1. Hepatology. 61:1920–1933. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Jiang T, Guan LY, Ye YS, Liu HY and Li R: MiR-874 inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting SOX12. Am J Cancer Res. 7:1310–1321. 2017.PubMed/NCBI

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December 2018
Volume 40 Issue 6

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Copy and paste a formatted citation
APA
Zhang, W., Liu, K., Liu, S., Ji, B., & Liu, Y. (2018). MicroRNA‑744 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12. Oncology Reports, 40, 3585-3592. https://doi.org/10.3892/or.2018.6774
MLA
Zhang, W., Liu, K., Liu, S., Ji, B., Liu, Y."MicroRNA‑744 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12". Oncology Reports 40.6 (2018): 3585-3592.
Chicago
Zhang, W., Liu, K., Liu, S., Ji, B., Liu, Y."MicroRNA‑744 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12". Oncology Reports 40, no. 6 (2018): 3585-3592. https://doi.org/10.3892/or.2018.6774