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

Research Paper

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

Zhou-Tong Dai1*, Yuan Xiang2*, Yuan-yuan Duan1*, Jun Wang1, Jia Peng Li1, Hui-Min Zhang1, Chao Cheng3✉, Qiong Wang1✉, Tong-Cun Zhang1,4✉, Xing-Hua Liao1✉

1. Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei, 430081, P.R. China.
2. Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Hubei, 430014, P.R. China.
3. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
4. Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tinajin, 300457, P.R. China.
* These authors contributed equally to the paper.

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Citation:
Dai ZT, Xiang Y, Duan Yy, Wang J, Li JP, Zhang HM, Cheng C, Wang Q, Zhang TC, Liao XH. MiR-17-5p and MKL-1 modulate stem cell characteristics of gastric cancer cells. Int J Biol Sci 2021; 17(9):2278-2293. doi:10.7150/ijbs.57338. Available from https://www.ijbs.com/v17p2278.htm

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