The lncRNA SCARNA2 mediates colorectal cancer chemoresistance through a conserved microRNA-342-3p target sequence

J Cell Physiol. 2019 Jul;234(7):10157-10165. doi: 10.1002/jcp.27684. Epub 2018 Nov 15.

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in numerous physiological and pathological processes, including cancer development and progression. However, the role and molecular mechanism of lncRNAs in resistance to chemotherapy of colorectal cancer (CRC) remain enigmatic. Here, we found that lncRNA small Cajal body-specific RNA 2 (SCARNA2) is expressed higher in CRC tissues than in adjacent normal tissues, and a robust expression of SCARNA2 is correlated with a bad prognosis of CRC patients after surgery. SCARNA2 overexpression significantly promoted chemoresistance in CRC cells, and downregulation of SCARNA2 obviously inhibited chemoresistance in vitro. SCARNA2 promotes chemotherapy resistance via competitively binding miR-342-3p to facilitate epidermal growth factor receptor (EGFR) and B-cell lymphoma 2 (BCL2) expression in CRC cells. Together, our results reveal a novel pathway that SCARNA2 regulates CRC chemoresistance through targeting miR-342-3p-EGFR/BCL2 pathway, providing a promising therapeutic target for CRC.

Keywords: CRC; SCARNA2; chemoresistance; lncRNA; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Conserved Sequence / genetics
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / biosynthesis
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • RNA, Long Noncoding / genetics*
  • Tumor Cells, Cultured

Substances

  • BCL2 protein, human
  • MIRN342 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • EGFR protein, human
  • ErbB Receptors