Frontiers in Oncology (May 2021)

uc.77- Downregulation Promotes Colorectal Cancer Cell Proliferation by Inhibiting FBXW8-Mediated CDK4 Protein Degradation

  • Zhijian Zheng,
  • Dan Hong,
  • Xiaodong Zhang,
  • Yixin Chang,
  • Ning Sun,
  • Zhenni Lin,
  • Hongyan Li,
  • Shirui Huang,
  • Ruirui Zhang,
  • Qipeng Xie,
  • Haishan Huang,
  • Honglei Jin

DOI
https://doi.org/10.3389/fonc.2021.673223
Journal volume & issue
Vol. 11

Abstract

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Transcribed ultraconserved regions (T-UCRs) are a new type of long non-coding RNA, and the UCR has 481 segments longer than 200 base pairs that are 100% conserved between humans, rats, and mice. T-UCRs involved in colorectal cancer (CRC) have not been studied in detail. We performed T-UCR microarray analysis and found that uc.77- was significantly downregulated in CRC tissues and cell lines. Ectopic expression of uc.77- significantly inhibited the proliferation of CRC cells in vitro and the growth of xenograft tumors in nude mice in vivo. Mechanistic studies showed that uc.77- competed with FBXW8 mRNA for binding to microRNA (miR)-4676-5p through a competing endogenous RNA mechanism and inhibited the proliferation of CRC cells by negatively regulating CDK4. The present findings highlight the role of the uc.77-/miR-4676-5p/FBXW8 axis in CRC and identify uc.77- as a potential novel target for the treatment of CRC.

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