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

被引:24
作者
Dai, Zhou-Tong [1 ]
Xiang, Yuan [2 ]
Duan, Yuan-yuan [1 ]
Wang, Jun [1 ]
Li, Jia Peng [1 ]
Zhang, Hui-Min [1 ]
Cheng, Chao [3 ]
Wang, Qiong [1 ]
Zhang, Tong-Cun [1 ,4 ]
Liao, Xing-Hua [1 ]
机构
[1] Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Med Lab, Wuhan 430014, Hubei, Peoples R China
[3] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastrointestinal Surg, Wuhan, Hubei, Peoples R China
[4] Tianjin Univ Sci & Technol, Coll Biotechnol, Key Lab Ind Fermentat Microbiol, Minist Educ & Tianjin, Tinajin 300457, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-17-5p; MKL-1; gastric cancer; stem cells; bioinformatics; EPITHELIAL-MESENCHYMAL TRANSITION; REGULATES SELF-RENEWAL; ACUTE MYELOID-LEUKEMIA; TRANSCRIPTION FACTOR; MRTF-A; MYOCARDIN; IDENTIFICATION; SUPPRESSION; METASTASIS; INHIBITION;
D O I
10.7150/ijbs.57338
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2278 / 2293
页数:16
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