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

Jiafu Zhao; Xiaoyan Ma; Houqiang Xu

doi:10.3892/ol.2022.13409

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

Oncol Lett. 2022 Jul 1;24(2):289. doi: 10.3892/ol.2022.13409. eCollection 2022 Aug.

Authors

Jiafu Zhao^{1

2}, Xiaoyan Ma^{1

3}, Houqiang Xu^{1

2}

Affiliations

¹ Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, Guizhou University, Guiyang, Guizhou 550025, P.R. China.
² College of Animal Science, Guizhou University, Guiyang, Guizhou 550025, P.R. China.
³ College of food and pharmaceutical engineering, Guizhou Institute of Technology, Guiyang, Guizhou 550003, P.R. China.

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.

Keywords: YWHAE; cell proliferation; metastatic CRPC; microRNA-29b-3p; regulatory axis.

Grants and funding

The present study was supported by the Natural Science Foundation of Guizhou Province [grant no. QKHJC (2020) 1Y085], the Natural Science Foundation of China (grant no. 31860242) and the Guizhou Province Science and Technology Plan Project [grant no. Guizhou Branch Platform Talents (2019) 3336].