4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 17, Issue 9, Pages 2278-2293

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/ijbs.57338

Keywords

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

Funding

  1. National Natural Science Foundation of China [31501149, 31770815, 31570764]
  2. Hubei Natural Science Foundation [2017CFB537]
  3. Educational Commission of Hubei [B2020001]
  4. Hubei Province Health and Family Planning Scientific Research Project [WJ2021Q051, WJ2019M255]
  5. Frontier project of applied basic research in Wuhan [2020020601012250]

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This study preliminarily explored the mechanism of miR-17/MKL-1 in gastric cancer stem cells, and verified the role of miR-17-5p and MKL-1 in promoting stem cell-like properties of gastric cancer through experiments. It was found that MKL-1 promotes expression by targeting miR-17, CD44 and EpCAM promoters, providing new insights for potential early diagnosis and/or molecular therapy of gastric cancer stem cells.
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.

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