Long noncoding RNA LINC00963 induces NOP2 expression by sponging tumor suppressor miR-542-3p to promote metastasis in prostate cancer.

Abstract

Metastatic disease caused by castration-resistant prostate cancer (CRPC) is the principal cause of prostate cancer (PCa)-related mortality. CRPC occurs within 2-3 years of initiation of androgen deprivation therapy (ADT), which is an important factor of influencing PCa metastasis. Recent studies have revealed that non-coding RNAs in PCa can enhance metastasis and progression, while the mechanisms are still unclear. In this study, we reported that the long noncoding RNA-LINC00963 was increased in CRPC tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of LINC00963 significantly decreased tumor suppressor miR-542-3p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. LINC00963 promotes and miR-542-3p inhibits metastasis. Furthermore, the expression levels of LINC00963 and miR-542-3p were positively and negatively associated with the expression of NOP2. We demonstrated that NOP2 promoted PCa by activating the epithelial-mesenchymal transition (EMT) pathway. For specific mechanism, dual luciferase reporter assays showed that miR-542-3p directly binds to both 3'-untranslated region (UTR) of LINC00963 and NOP2 mRNA. Taken together, our results show that LINC00963 acts as an inducer of PCa metastasis by binding miR-542-3p, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.

• Authors: Feng Sun, Ke Wu, Zhixian Yao, Xingyu Mu, Zhong Zheng, Menghao Sun, Yong Wang, Zhihong Liu, Yiyong Zhu
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 12 Pg. 11500-11516 (06 17 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 32554858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN542 microRNA, human
• MIRN542 microRNA, mouse
• MicroRNAs
• Nuclear Proteins
• RNA, Long Noncoding
• long non-coding RNA LINC00963, human
• NOP2 protein, human
• Nop2 protein, mouse
• Protein Methyltransferases
• tRNA Methyltransferases

Topics

• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Male
• Mice
• Mice, Transgenic
• MicroRNAs (agonists, antagonists & inhibitors, metabolism)
• Neoplasm Metastasis (genetics)
• Nuclear Proteins (genetics)
• Prostate (pathology)
• Prostatic Neoplasms, Castration-Resistant (genetics, pathology)
• Protein Methyltransferases (genetics)
• RNA, Long Noncoding (genetics, metabolism)
• RNA-Seq
• Xenograft Model Antitumor Assays
• tRNA Methyltransferases (genetics)