MicroRNA-539 inhibiting the occurrence and development of hepatocellular carcinoma by targeting E2F transcription factor 3

DENG Xue-jun GONG Shao-xin* YANG Sheng-hui HUANG Li-rong ZHOU Fang

doi:10.16098/j.issn.0529-1356.2018.04.009

PDF(307 KB)

Acta Anatomica Sinica ›› 2018, Vol. 49 ›› Issue (4) : 469-474. DOI: 10.16098/j.issn.0529-1356.2018.04.009

MicroRNA-539 inhibiting the occurrence and development of hepatocellular carcinoma by targeting E2F transcription factor 3

DENG Xue-jun¹ GONG Shao-xin ^1* YANG Sheng-hui² HUANG Li-rong³ZHOU Fang³

Author information +

History +

Abstract

Objective To investigate the expression of microRNA-539 (miR-539) in hepatocellular carcinoma (HCC) and the possible mechanism of miR-539 inhibition cancer cells. Methods Ninety cases of liver cancer patients after liver cancer tissue and adjacent tissue specimens were collected, and the expression of miR-539 in clinical tissues was detected by Real-time PCR. MiR-539 mimics was transfected into QGY-7701, Huh7 and PCL/PRF5 hepatoma cells, and the expression of miR-539 was detected by Real-time PCR. The effect of miR-539 on the proliferation of HCC cells was detected by MTT assay. The effect of miR-539 on the apoptosis of hepatocellular carcinoma cells was detected by flow cytometry. The effect of miR-539 on the expression of E2F transcription factor 3(E2F3) protein in hepatocarcinoma cells was detected by Western blotting. Results The expression of miR-539 in hepatocellular carcinoma was significantly lower than that in adjacent tissues. The expression of miR-539 was not correlated with sex, age and histological differentiation of hepatocellular carcinoma (P>0.05). The expression of miR-539 was correlated with tumor diameter and lymph node metastasis (P<0.05). The expression of miR-539 in miR-539 mimics group was significantly higher than that in blank group and miR-539 NC group (P<0.05). In QGY-7701 cells, overexpression of miR-539 significantly inhibited cell proliferation (P<0.05), decreased E2F3 protein expression (P<0.05), but was no significant effect on apoptosis (P>0.05). Conclusion miR-539 is a tumor suppressor factor in the development of hepatocellular carcinoma, which may inhibit the proliferation of cancer cells through the down-regulation of E2F3 protein level.

Key words

Hepatocellular carcinoma / microRNA-539 / Transcription factor / Proliferation / Real-time PCR / Western blotting / Human

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

DENG Xue-jun GONG Shao-xin YANG Sheng-hui HUANG Li-rong ZHOU Fang. MicroRNA-539 inhibiting the occurrence and development of hepatocellular carcinoma by targeting E2F transcription factor 3[J]. Acta Anatomica Sinica. 2018, 49(4): 469-474 https://doi.org/10.16098/j.issn.0529-1356.2018.04.009

References

［1］ Wei KR, Yu X, Zheng RS, et al. Incidence and mortality of liver cancer in China, 2010［J］. Chin J Cancer, 2014, 33(8):388-394.

［2］ Zhang JL, Zhai B, Fang TSh, et al. Progress in the treatment of advanced liver cancer and recurrent liver cancer ［J］. Progress in Modern Biomedicine, 2016, 16 (2): 358-361. (in Chinese)

张金梁, 翟博, 方泰石, 等. 晚期肝癌和复发性肝癌治疗的研究进展［J］. 现代生物医学进展, 2016, 16(2):358-361.

［3］ Altekruse SF, Henley SJ, Cucinelli JE, et al. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States［J］. Am J Gastroenterol, 2014, 109(4):542-553.

［4］ Vitale A, Burra P, Frigo AC, et al. Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study［J］. J Hepatol, 2015, 62(3):617-624.

［5］ Fan BL, Ji XH, Zhu WL. Effects of MiR-100 on mitotic arrest and Pololike kinase 1 protein expression in hepatocellular carcinoma cells［J］. Acta Acatomica Sinica, 2014,45(1):70-73. (in Chinese)

范秉琳, 嵇晓辉, 朱武凌. MiR-100对肝癌细胞有丝分裂阻滞及Polo样激酶1蛋白表达的作用［J］. 解剖学报, 2014, 45(1):70-73.

［6］ Pipan Ⅴ, Zorc M, Kunej T. MicroRNA polymorphisms in cancer: a literature analysis［J］. Cancers, 2015, 7(3):1806-1814.

［7］ Reddy KB. MicroRNA (miRNA) in cancer［J］. Cancer Cell Int, 2015, 15(1):1-6.

［8］ Utsunomiya T, Ishikawa D, Asanoma M, et al. Specific miRNA expression profiles of nontumor liver tissue predict a risk for recurrence of hepatocellular carcinoma［J］. Hepatol Res, 2014, 44(6):631-638.

［9］ Gu L, Sun W. MiR-539 inhibits thyroid cancer cell migration and invasion by directly targeting CARMA1［J］. Biochem Biophys Res Commun, 2015, 464(4):1128-1133.

［10］ Nelson HC, Kazuaki C. MicroRNAs as Biomarkers for liver disease and hepatocellular carcinoma［J］. Int J Mol Sci, 2016, 17(3):280.

［11］ Shibata T, Aburatani H. Exploration of liver cancer genomes［J］. Nat Rev Gastroenterol Hepatol, 2014, 11(6):340-349.

［12］ Tai CJ, Huang MT, Wu CH, et al. Contrast-enhanced ultrasound and computed tomography assessment of hepatocellular carcinoma after transcatheter arterial chemo-embolization: a systematic review［J］. J Gastrointestin Liver Dis, 2016, 25(4):499-507.

［13］ Zhang J, Zhang JP. Research progress on hepatocellular carcinoma stem cells［J］. Journal of Hainan Medical University, 2014, 20 (6): 870-872. (in Chinese)

张津, 张俊平. 肝癌干细胞的研究进展［J］. 海南医学院学报, 2014, 20(6):870-872.

［14］ He S, Zhang DC, Wei C. MicroRNAs as biomarkers for hepatocellular carcinoma diagnosis and prognosis［J］. Clin Res Hepatol Gastroenterol, 2015, 39(4):426-434.

［15］ Zeng X, Yin F, Liu X, et al. Upregulation of E2F transcription factor 3 is associated with poor prognosis in hepatocellular carcinoma［J］. Oncol Rep, 2014, 31(3):1139-1146.

［16］ Miles WO, Tsch?p K, Herr A, et al. Pumilio facilitates miRNA regulation of the E2F3 oncogene［J］. Genes Dev, 2012, 26(4):356-368.

［17］ Huang X, Zeng Y, Wang X, et al. FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway［J］. Biochem Biophys Res Commun, 2016, 474(2):351-356.

［18］ Cao T, Li H, Hu Y, et al. miR-144 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting E2F3［J］. Tumor Biol, 2014, 35(11):10759-10764.

［19］ Yang Y, Chang S, Zhao Z, et al. MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3［J］. Oncol Lett, 2015, 10(6):3779-3784.

［20］ Liu Y, Liang ChH, Li ZZh, et al. The role of microRNA in the occurrence and development of primary hepatocellular carcinoma and its clinical significance［J］. The World Clinical Medicine, 2017,11 (13): 110. (in Chinese)

刘勇, 梁长华, 李增志, 等. MicroRNA在原发性肝细胞肝癌发生与发展中的作用及临床意义［J］. 世界临床医学, 2017, 11(13):110.