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:10.3389/fonc.2021.673223

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

Front Oncol. 2021 May 19:11:673223. doi: 10.3389/fonc.2021.673223. eCollection 2021.

Authors

Affiliations

¹ Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
² Department of Colorectal Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

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.

Keywords: CDK4; FBXW8; colorectal cancer; miR-4676-5p; uc.77-.