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

Aging (Albany NY). 2020 Jun 17;12(12):11500-11516. doi: 10.18632/aging.103236. Epub 2020 Jun 17.


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.

Keywords: NOP2; lncRNA LINC00963; metastasis; miR-542-3p; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis / genetics
  • Nuclear Proteins / genetics*
  • Prostate / pathology
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Protein Methyltransferases / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Seq
  • Xenograft Model Antitumor Assays
  • tRNA Methyltransferases / genetics*


  • 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