Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3-c-Myc axis

Oncogene. 2020 May;39(19):3926-3938. doi: 10.1038/s41388-020-1266-8. Epub 2020 Mar 20.

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer long noncoding RNAs (lncRNAs) have been known to play crucial roles in cancer development and progression by regulating chromatin dynamics and gene expression. However, only a few lncRNAs with annotated functions in the progression of colorectal cancer (CRC) have been identified to date. In the present study, the expression of lncCMPK2 was upregulated in CRC tissues and positively correlated with clinical stages and lymphatic metastasis. The overexpression of lncCMPK2 promoted the proliferation and cell cycle transition of CRC cells. Conversely, the silencing of lncCMPK2 restricted cell proliferation both in vitro and in vivo. lncCMPK2 was localized to the nucleus of CRC cells, bound to far upstream element binding protein 3 (FUBP3), and guided FUBP3 to the far upstream element (FUSE) of the c-Myc gene to activate transcription. lncCMPK2 also stabilized FUBP3. These results provide novel insights into the functional mechanism of lncCMPK2 in CRC progression and highlight its potential as a biomarker of advanced CRC and therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • HCT116 Cells
  • Heterografts
  • Humans
  • Mice
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • FUBP3 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • Transcription Factors