LncRNA SNHG16 Promotes Hepatocellular Carcinoma Proliferation, Migration and Invasion by Regulating MiR-186 Expression

Overview

Journal J Cancer

Specialty Oncology

Date 2019 Jul 12

PMID 31293662

Citations 33

Authors

Hang Chen

Molin Li

Ping Huang

Affiliations

Soon will be listed here.

Abstract

Long non-coding RNA (lncRNA) and microRNA (miRNA) play an important role in genesis and progression of tumors. The aim of this study was to explore the expression, biological function and molecular mechanism of small nucleolar RNA host gene 16 (SNHG16) in HCC. RT-qPCR was conducted to evaluate the expression level of SNHG16 in HCC tissues and cell lines. Our findings showed for the first time that SNHG16 was up-regulated in HCC tissues and cell lines. The expression of SNHG16 in cancer tissues was highly correlated with tumor size, TNM stage, ALT expression level and HBV DNA level. Moreover, cell proliferation, migration and invasion were detected by CCK-8 assay, transwell migration assay and transwell invasion assay, respectively. Xenograft tumor experiment was used to determine the biological function of SNHG16 . As revealed by our data, SNHG16 accelerated the proliferation, migration and invasion of HCC cell. SNHG16 facilitated tumor formation . Next, the relationship between SNHG16, miR-186 and ROCK1 were analyzed using bioinformatics analysis, qRT-PCR, luciferase reporter assay and western blot. Further molecular mechanism studies reported that the expression of SNHG16 was negatively correlated with the level of miR-186 and SNHG16 directly bound to miR-186. SNHG16 and miR-186 repressed each other. Notably, rescue experiments were conducted and showed that miR-186 reversed the effect of SNHG16 on cell. Taken together, SNHG16 promoted HCC cell proliferation, migration and invasion by functioning as a competitive endogenous RNA (ceRNA) to negatively regulate miR-186 expression. Our data suggested that SNHG16 might be a potential biomarker and a new therapeutic target for HCC.

Citing Articles

Molecular mechanisms underlying roles of long non-coding RNA small nucleolar RNA host gene 16 in digestive system cancers.

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References

Cho W . MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2009; 42(8):1273-81. DOI: 10.1016/j.biocel.2009.12.014. View

Krol J, Loedige I, Filipowicz W . The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010; 11(9):597-610. DOI: 10.1038/nrg2843. View

Wang D, Qiu C, Zhang H, Wang J, Cui Q, Yin Y . Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets. PLoS One. 2010; 5(9). PMC: 2948010. DOI: 10.1371/journal.pone.0013067. View

Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S . microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 2011; 30(47):4750-6. PMC: 4292930. DOI: 10.1038/onc.2011.193. View

Tay Y, Kats L, Salmena L, Weiss D, Tan S, Ala U . Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011; 147(2):344-57. PMC: 3235920. DOI: 10.1016/j.cell.2011.09.029. View

Forner A, Llovet J, Bruix J . Hepatocellular carcinoma. Lancet. 2012; 379(9822):1245-55. DOI: 10.1016/S0140-6736(11)61347-0. View

Morgan-Fisher M, Wewer U, Yoneda A . Regulation of ROCK activity in cancer. J Histochem Cytochem. 2012; 61(3):185-98. PMC: 3636696. DOI: 10.1369/0022155412470834. View

Cai J, Wu J, Zhang H, Fang L, Huang Y, Yang Y . miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation. Cancer Res. 2012; 73(2):756-66. DOI: 10.1158/0008-5472.CAN-12-2651. View

Leucci E, Patella F, Waage J, Holmstrom K, Lindow M, Porse B . microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep. 2013; 3:2535. PMC: 3756333. DOI: 10.1038/srep02535. View

10.

Guo G, Kang Q, Zhu X, Chen Q, Wang X, Chen Y . A long noncoding RNA critically regulates Bcr-Abl-mediated cellular transformation by acting as a competitive endogenous RNA. Oncogene. 2014; 34(14):1768-79. DOI: 10.1038/onc.2014.131. View

11.

Cui G, Cui M, Li Y, Liang Y, Li W, Guo H . MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells. Tumour Biol. 2014; 35(9):8933-7. DOI: 10.1007/s13277-014-2168-6. View

12.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

13.

Khoury S, Tran N . Circulating microRNAs: potential biomarkers for common malignancies. Biomark Med. 2015; 9(2):131-51. DOI: 10.2217/bmm.14.102. View

14.

Wang Y, He L, Du Y, Zhu P, Huang G, Luo J . The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell. 2015; 16(4):413-25. DOI: 10.1016/j.stem.2015.03.003. View

15.

He W, Feng J, Zhang Y, Wang Y, Zang W, Zhao G . microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2. Lab Invest. 2015; 96(3):317-24. DOI: 10.1038/labinvest.2015.134. View

16.

Sun K, Jiao J, Chen S, Liu B, Zhao Y . MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1. J Ovarian Res. 2015; 8:80. PMC: 4667519. DOI: 10.1186/s13048-015-0207-6. View

17.

Yuan J, Yue H, Zhang M, Luo J, Liu L, Wu W . Transcriptional profiling analysis and functional prediction of long noncoding RNAs in cancer. Oncotarget. 2016; 7(7):8131-42. PMC: 4884981. DOI: 10.18632/oncotarget.6993. View

18.

Thomson D, Dinger M . Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016; 17(5):272-83. DOI: 10.1038/nrg.2016.20. View

19.

Christensen L, True K, Hamilton M, Nielsen M, Damas N, Damgaard C . SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism. Mol Oncol. 2016; 10(8):1266-82. PMC: 5423192. DOI: 10.1016/j.molonc.2016.06.003. View

20.

Hua X, Xiao Y, Pan W, Li M, Huang X, Liao Z . miR-186 inhibits cell proliferation of prostate cancer by targeting GOLPH3. Am J Cancer Res. 2016; 6(8):1650-60. PMC: 5004070. View