Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating β-catenin signaling

Cell Cycle. 2018;17(13):1602-1613. doi: 10.1080/15384101.2018.1475825. Epub 2018 Aug 2.

Abstract

Small RNAs play an important role in gene regulatory networks. The gene suppressive effect of small RNAs was previously the dominant focus of studies, but during the recent decade, small RNA-induced gene activation has been reported and has become a notable gene manipulation technique. In this study, a putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA (dsRNA-915) into castration-resistant prostate cancer (CRPC) cells. Unique dynamics associated with the gene upregulation phenomenon was observed. Following gene activation, cell proliferation and motility were suppressed in vitro. Downregulation of Wnt/β-catenin signaling was observed during the activation period, and the impairment of β-catenin degradation reversed the tumor suppressor effects of INTS6. These results suggest the potential application of small activating RNAs in targeted gene therapy for CRPC.

Keywords: INTS6; RNA activation; castration-resistant prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Base Sequence
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival / genetics
  • Clone Cells
  • Down-Regulation / genetics
  • Epigenesis, Genetic
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Promoter Regions, Genetic / genetics
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • RNA, Double-Stranded / metabolism*
  • RNA-Binding Proteins
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Time Factors
  • Transcriptional Activation
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Up-Regulation / genetics*
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • INTS6 protein, human
  • RNA, Double-Stranded
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • Tumor Suppressor Proteins
  • beta Catenin

Grants and funding

This work was supported by the National Natural Science Foundation of China [81372773];Natural Science Foundation of Zhejiang Province [LY16H160015];Natural Science Foundation of Zhejiang Province [LQ16H160011];