Elevated microRNA-130b-5p or silenced ELK1 inhibits self-renewal ability, proliferation, migration, and invasion abilities, and promotes apoptosis of cervical cancer stem cells

IUBMB Life. 2021 Jan;73(1):118-129. doi: 10.1002/iub.2409. Epub 2020 Dec 8.

Abstract

Cervical cancer (CC) is the most familiar gynecological malignancy. With the poor prognosis of CC patients, this study explored the effect of microRNA (miR)-130b-5p targeting ELK1 expression on self-renewal ability and stemness of CC stem cells. The tissues of patients with CC or cervical benign lesions were collected. MiR-130b-5p and ELK1 expression was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. Human CC cell line Hela was cultured and the induced CC stem cells were introduced with miR-130b-5p mimic or silenced ELK1 to figure their roles in self-renewal ability, stemness, colony formation, proliferation, migration, invasion abilities, and apoptosis of CC stem cells. Tumor growth was detected in nude mice in vivo. The targeting relationship between miR-130b-5p and ELK1 was analyzed using bioinformatic prediction and dual luciferase reporter gene assay. Decreased miR-130b-5p and elevated ELK1 existed in CC tissues of patients. Up-regulated miR-130b-5p decreased ELK1 expression in CC stem cells. Elevated miR-130b-5p or silenced ELK1 inhibited self-renewal ability and stemness, colony formation, proliferation, migration and invasion abilities, promoted apoptosis of CC stem cells, as well as decreased the weight and volume of tumor in nude mice. ELK1 was found to be targeted by miR-130b-5p. Overexpression ELK1 effectively reversed the cellular phenotypic changes and tumor formation in vivo caused by up-regulation of miR-130b-5p. We conclude that up-regulated miR-130b-5p or silenced ELK1 inhibits CC stem cell growth.

Keywords: ELK1; MicroRNA-130b-5p; apoptosis; cervical cancer; colony formation; invasion; migration; proliferation; self-renewal ability; stem cells; stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Cell Self Renewal*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays
  • ets-Domain Protein Elk-1 / genetics
  • ets-Domain Protein Elk-1 / metabolism*

Substances

  • Biomarkers, Tumor
  • ELK1 protein, human
  • MIRN130 microRNA, human
  • MicroRNAs
  • ets-Domain Protein Elk-1