The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression.

Abstract

For human prostate cancer, the chromosome 8p21 locus, which contains NKX3.1 and the microRNA (miR)-3622 family (miR-3622a/b), is a frequently deleted region. Thus, miR-3622 is proposed as a suppressor for prostate cancer, but its role remains debatable. In the present study, we found that expression of miR-3622a was lower, whereas expression of miR-3622b-3p was higher in human prostate cancer tissues than in normal prostate tissues. miR-3622a-3p inhibited cell migration and invasion of human prostate cancer cells, whereas miR-3622b-3p facilitated cell proliferation, migration, and invasion. To address the opposing roles of miR-3622 family members in various human prostate cancer cell lines, we knocked out (KO) endogenous miR-3622, including both miR-3622a/b. Our results showed that miR-3622 KO reduced cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Functional analyses revealed that miR-3622 regulated the p53-downstream gene network, including AIFM2, c-MYC, and p21, to control apoptosis and the cell cycle. Furthermore, using CRISPR interference, miRNA/mRNA immunoprecipitation assays, and dual-luciferase assays, we established that AIFM2, a direct target of miR-3622b-3p, is responsible for miR-3622 KO-induced apoptosis. We identified an miR-3622-AIFM2 axis that contributes to oncogenic function during tumor progression. In addition, miR-3622 KO inhibited the epithelial-mesenchymal transition involved in prostate cancer metastasis via upregulation of vimentin. The results show that miR-3622b-3p is upregulated in human prostate cancers and has an oncogenic function in tumor progression and metastasis via repression of p53 signaling, especially through an miR-3622-AIFM2 axis. In contrast, for human prostate cancer, deletion of the miR-3622 locus at 8p21 reduced the oncogenic effects on tumor progression and metastasis.

• Authors: Yue Zhang, Zhifang Xu, Wen Wen, Zhichao Liu, Chao Zhang, Ming Li, Fengping Hu, Shi Wei, Sejong Bae, Jiangbing Zhou, Runhua Liu, Lizhong Wang
• Journal: Oncogene (Oncogene) Vol. 41 Issue 23 Pg. 3186-3196 (06 2022) ISSN: 1476-5594 [Electronic] England
• PMID: 35501464 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• MicroRNAs
• Tumor Suppressor Protein p53

Topics

• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Chromosomes, Human, Pair 8
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• Male
• MicroRNAs (genetics, metabolism)
• Prostate (pathology)
• Prostatic Neoplasms (genetics, pathology)
• Tumor Suppressor Protein p53 (genetics, metabolism)