miR-216b-5p is Down-Regulated in Human Breast Cancer and Inhibits Proliferation and Progression by Targeting HDAC8 Oncogene [article]

Mohammad-Nazir Menbari, Karim Rahimi, Abbas Ahmadi, Samira Mohammadi-Yeganeh, Anvar Elyasi, Nikoo Darvishi, Vahedeh Hosseini, Mohammad Abdi
2018 bioRxiv   pre-print
Previous studies showed the role of histone deacetylases (HDACs) on the progression of some malignancies. Recently, there is more attention to therapeutic applications of epigenetic factors such as microRNAs (miRs). To the best of our knowledge, there are no other results regarding the contribution of miR-216b-5p and its potential target, HDAC8, in the progression of cancer. Aim: In the present study, we investigated the role of miR-216b-5p on HDAC8 and there following impacts on breast cancer
more » ... s on breast cancer (BC) progression. Methods: Human BC specimens and noncancerous tissues were acquired from Iran Tumor Bank (I.T.B). The MDA-MB-231, MCF-7 and MCF-10A BC cell lines were also prepared. The tissue and cell line expression levels of miR-216b-5p and HDAC8 were determined by quantitative real-time PCR (qPCR). Protein levels of HDAC8 were also measured by Western blotting assay. The cell cycle, cell proliferation and colony formation assay were determined and the role of HDAC8 was investigated using a knockout vector. Targeting the 3' untranslated region (3'UTR) of HDAC8 by miR-216b-5p were confirmed using a luciferase reporter assay. Results: Our results show the significant decline in miR-216b-5p and highly increase in HDAC8 levels in human breast cancer tissues and cell lines. Overexpression of miR-216b-5p in BC cell lines inhibited cellular proliferation and progression and inhibition of miR-216b-5p reverse these effects. We also confirmed that HDAC8 is directly down-regulated by miR-216b-5p. Knockout of HDAC8 had also the effects as miR-216b-5p overexpression. Furthermore, we found that lower levels of miR-216b-5p are negatively correlated with lymph node metastasis and advanced tumor size. Conclusion: Taken together, our data showed that targeted overexpression of miR-216b-5p can suppress the growth of BC cells down-regulation of HDAC8. Therefore, inhibition of HDAC8 by miR-216b-5p will be helpful in developing newer therapies for the effective treatment of BC.
doi:10.1101/499905 fatcat:o6rt4iykcbay5jtems37wqnaey