Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway

Oncol Res. 2018 Jan 19;26(1):131-143. doi: 10.3727/096504017X14944585873631. Epub 2017 May 11.

Abstract

Prostate cancer has become the most commonly diagnosed and the second leading cause of cancer-related deaths in males. The long noncoding RNA second chromosome locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in a subset of prostate cancer. However, the significance and mechanism of SChLAP1 in prostate cancer are not well known. In this study, we explored the role of SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1 expression was significantly increased in prostate cancer cells and tissues. Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and invasion in vitro and in vivo. In addition, a potential bonding site between miR-198 and SChLAP1 was predicted, and a low expression of miR-198 was found in prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased the expression of miR-198, and SChLAP1 overexpression markedly decreased it, indicating that SChLAP1 acted as a negative regulator in the expression of miR-198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and subsequently modulated the MAPK1 signaling pathway in prostate cancer. In conclusion, our study has identified a novel pathway through which SChLAP1 exerts its oncogenic role in prostate cancer at the level of miRNAs and provided a molecular basis for potential applications of SChLAP1 in the prognosis and treatment of prostate cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Neoplasm Invasiveness / genetics
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • RNA, Long Noncoding / genetics*

Substances

  • MIRN198 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SChLAP1 long noncoding RNA
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1