miR-29b-3p inhibits 22Rv1 prostate cancer cell proliferation through the YWHAE/BCL-2 regulatory axis

miR-29b-3p通过YWHAE/BCL-2调节轴抑制22Rv1前列腺癌细胞增殖

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作者:Jiafu Zhao, Xiaoyan Ma, Houqiang Xu

Abstract

Prostate cancer (PCa) is one of the most common malignant tumours in the world and seriously affects health of men. Studies have shown that microRNA (miR)-29b-3p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE) play important roles in influencing the proliferation and apoptosis of PCa cells. However, the molecular mechanism of miR-29b-3p and YWHAE in the proliferation and apoptosis of PCa cells remains unclear. In the present study, bioinformatics as well as in vivo and in vitro experiments were used to predict and verify the targeting relationship between YWHAE and mir-29B-3p and investigate the potential roles of YWHAE and mir-29b-3p in the proliferation and apoptosis of 22RV1 cells. Using bioinformatics and a double luciferase system assay, it was confirmed that miR-29b-3p can target YWHAE 3'untranslated region and affect the expression of YWHAE, suggesting that miR-29b-3p may be a potential miRNA of YWHAE. Reverse transcription-quantitative PCR, Cell Counting Kit-8, Transwell and cell scratch assays showed that miR-29b-3p significantly inhibited the proliferation, invasion and migration of 22Rv1 cells (P<0.01). Rescue experiments demonstrated that YWHAE gene introduction reversed the inhibitory effect of miR-29b-3p on 22Rv1 cells. Western blotting revealed that the upregulation of miR-29b-3p inhibited YWHAE expression, resulting in a very significant decrease in the ratio of p-BAD/BAD and full-length caspase 3/cleaved caspase 3 (P<0.01) and an extremely significant increase in the ratio of BAX/BCL-2 (P<0.01). A tumourigenesis test in nude mice in vivo confirmed that the upregulation of miR-29b-3p inhibited tumour growth by targeting YWHAE. The present experiments confirmed that miR-29b-3p plays a tumour suppressor role in 22Rv1 PCa cells, and the YWHAE/BCL-2 regulatory axis plays a vital role in miR-29b-3p regulating the proliferation and apoptosis of 22Rv1 cells. These results may provide a theoretical basis for the diagnosis and targeted treatment of PCa.

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