Down-regulated Circ_0000190 promotes cervical cancer by facilitating the activity of proto-oncogene protein EIF4E

Cell Cycle. 2022 Jul;21(13):1349-1359. doi: 10.1080/15384101.2021.2018212. Epub 2022 Apr 13.

Abstract

Circular RNAs (circRNAs), a new class of non-coding RNAs, have been recently confirmed to regulate cell development, functions and certain types of pathological responses. In addition, it has been proved that circ_0000190 can serve as a tumor suppressor in several cancers. However, the underlying mechanism and biological functions of it in cervical cancer (CC) remain to be revealed. In our study, relative expression of indicated molecules was detected by RT-qPCR analysis. Loss-of-function and gain-of-function experiments were conducted to detect cell functions. Mechanism experiments including RIP assay, luciferase reporter assay and pull down assay were applied to verify the interaction among the indicated molecules. Overexpressed circ_0000190 attenuated CC progression in vitro and in vivo. Circ_0000190 functioned through the modulation of miR-1252-5p/EIF4EBP2 axis. Rescue experiments found that miR-1252-5p overexpression or EIF4EBP2 knockdown could reverse the influence on CC cells caused by circ_0000190 overexpression. Interestingly, it was found that EIF4EBP2 could bind to proto-oncogene eIF4E and prevent eIF4E from forming into complex and functioning. Circ_0000190 served as a tumor suppressor in CC and down-regulated circ_0000190 expression could weaken the binding ability of EIF4EBP2 to eIF4E thus leading to CC tumorigenesis. In our investigation, a novel tumor suppressive gene circ_0000190 was recognized, which could be treated as a promising biomarker for the diagnosis of CC.

Keywords: Circ_0000190; EIF4EBP2; ceRNA; cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Eukaryotic Initiation Factor-4E* / genetics
  • Eukaryotic Initiation Factor-4E* / metabolism
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Proto-Oncogenes
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • EIF4E protein, human
  • Eukaryotic Initiation Factor-4E
  • MicroRNAs
  • Oncogene Proteins
  • RNA, Circular

Grants and funding

The study was supported by 2020 “Xinglin scholar” Subject Talent Research Promotion Plan - based on data mining technology to study the medication rule of Sichuan Traditional Chinese medicine in the diagnosis and treatment of infertility (ZRQN2020016).