MiR-17-5p and MKL-1 modulate stem cell characteristics of gastric cancer cells

Int J Biol Sci. 2021 Jun 4;17(9):2278-2293. doi: 10.7150/ijbs.57338. eCollection 2021.

Abstract

Effectively targeting cancer stem cells to treat cancer has great therapeutic prospects. However, the effect of microRNA miR-17/MKL-1 on gastric cancer stem cells has not been studied yet. This study preliminarily explored the mechanism of miR-17/MKL-1 in gastric cancer stem cells. Many previous reports have indicated that microRNA and EMT regulated cancer stem cell characteristics, and miR-17 and MKL-1 were involved as a critical gene in migration and invasion in the EMT pathway. Through RT-PCR, Western Blot, flow cytometry, immunofluorescence, sphere formation xenograft tumor assays and drug resistance, the role of miR-17-5p and MKL-1 on promoting stem cell-like properties of gastric cancer were verified in vivo and vitro. Next, MKL-1 targets CD44, EpCAM, and miR -17-5p promoter verified by luciferase assay and ChIP. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. It is found that MKL-1 promotes expression by targeting miR-17, CD44 and EpCAM promoters. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. These findings reveal new regulatory signaling pathways for gastric cancer stem cells, thus it give new insights on potential early diagnosis and/or molecular therapy for gastric cancer.

Keywords: MKL-1; bioinformatics.; gastric cancer; miR-17-5p; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Promoter Regions, Genetic
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • MIRN17 microRNA, human
  • MRTFA protein, human
  • MicroRNAs
  • Trans-Activators