Silencing of circular RNA_0000326 inhibits cervical cancer cell proliferation, migration and invasion by boosting microRNA-338-3p-dependent down-regulation of CDK4

Aging (Albany NY). 2021 Mar 17;13(6):9119-9134. doi: 10.18632/aging.103711. Epub 2021 Mar 17.

Abstract

Cervical cancer is one of the leading causes of cancer-related death among women, which is attributed partly by limited treatment options. Recent studies have provided in-depth explanations regarding the role of circular RNA in cancers. We aimed to investigate the role of circular RNA_0000326 in cervical cancer. Bioinformatics analysis revealed a high circ_0000326 expression in cervical cancer. Cervical cancer cells and tissues were also observed to have elevated levels of circ_0000326 and the upregulation of circ_0000326 depended on the stage of cancer. Transfection with siRNA of circ_0000326 resulted in the inhibition of proliferation, migration and cell cycle of cancer cells. Interestingly, we confirmed that circ_0000326 served as a sponge for microRNA-338-3p and that the miRNA bound to Cyclin-dependent kinase 4. In the presence of microRNA-338-3p mimic or silencing of circ_0000326, Cyclin-dependent kinase 4 expression was decreased. Transfection with microRNA-338-3p mimic inhibited cell clone formation and proliferation. Moreover, in vivo experiment revealed that the injection of shRNA-circ_0000326 lentivirus suppressed tumor growth and decreased Cyclin-dependent kinase 4 expression. Taken altogether, our results showed that circ_0000326 exerted oncogenic effects on cervical cancer by upregulating Cyclin-dependent kinase 4 via sponging microRNA-338-3p. This systematic investigation on circ_0000326 could provide further insight into cervical cancer.

Keywords: cervical cancer; circ_0000326; circular RNA; cyclin-dependent kinase 4; microRNA-338-3p.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Cyclin-Dependent Kinase 4 / genetics*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • RNA, Circular
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • MicroRNAs
  • Mirn338 microRNA, mouse
  • RNA, Circular
  • Cyclin-Dependent Kinase 4