Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p
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MicroRNAs (miRNAs) play vital roles in cell proliferation, differentiation and apoptosis in hepatocellular carcinoma (HCC). miR-26b has been confirmed as an important regulator in carcinogenesis and other pathological processes. miR-26b-5p is one member of the mature miR-26 family, and its functional role in proliferation, angiogenesis and apoptosis in HCC remains unknown. Here, we demonstrate that miR-26b-5p expression was significantly decreased in HCC tissues and HCC cell lines compared with normal liver tissues and liver cells by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between miR-26b-5p and the clinical characteristics of HCC patients were further analysed, and miR-26b-5p was positively correlated with the differentiation of HCC cells. Computational searches were further used to identify the downstream targets and signalling pathways of miR-26b-5p in HCC cells. Cell viability, proliferation and tube formation abilities were assessed by scrape, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and three-dimensional culture assays to confirm that miR-26b-5p inhibited HCC cell growth and impaired the tube formation ability of the HCC cells. Both in vitro and in vivo studies showed that miR-26b-5p could suppress vascular mimicry (VM) and angiogenesis by down-regulating the expression of VE-cadherin, Snail and MMP2 and could inhibit the apoptosis of HCC cells. Using mouse models, we revealed that tumours derived from miR-26b-5p-expressing HCC cells displayed a significant decrease in microvessel density compared with those derived from control cells. Therefore, our data provide further insight into the role of miR-26b-5p as a negative regulator of proliferation, angiogenesis, and apoptosis in HCC.
KeywordsmiR-26b-5p Angiogenesis Apoptosis Hepatocellular carcinoma
This study was funded by the Key project of the National Natural Science Foundation of China (no. 81230050), the National Natural Science Foundation of China (no. 81172046, no. 81173091 and no. 81301813), the Key project of the Tianjin Natural Science Foundation (no. 12JCZDJC23600) and the project of the Tianjin Natural Science Foundation (No. 14JCYBJC27700).
Compliance with ethical standards
Conflicts of interest
The authors declare no conflict of interest.
- 9.Kim HS, Shen, Park S, Lee KS, SJ Park, Y-K Kang, et al. MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer. Oncotarget. 2015;6(10).Google Scholar
- 11.Yan Y, Luo YC, Wan HY, Wang J, Zhang PP, Liu M, et al. MicroRNA-10a is involved in the metastatic process by regulating Eph tyrosine kinase receptor A4-mediated epithelial-mesenchymal transition and adhesion in hepatoma cells. Hepatology. 2013;57(2):667–77. doi: 10.1002/hep.26071.CrossRefPubMedGoogle Scholar
- 14.Keklikoglou I, Hosaka K, Bender C, Bott A, Koerner C, Mitra D, et al. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes. Oncogene. 2015;34(37):4867–78. doi: 10.1038/onc.2014.408.CrossRefPubMedGoogle Scholar
- 15.Zhao N, Wang RZ, Zhou LJ, Zhu Y, Gong J, Zhuang SM. MicroRNA-26b suppresses the NF-kB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3. Mol Cancer. 2014;13. doi: 10.1186/1476-4598-13-35.
- 25.Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and Molecular Targeting Therapy in Cancer. Biomed Res Int. 2014;Artn 150845. doi:10.1155/2014/150845.Google Scholar
- 31.Wang J, Huang R, Chu ES, Lan HY, Chen H-Y, JJ Sung, et al. microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway. Oncotarget. 2015;6(9).Google Scholar