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MiR-17-5p and MKL-1 modulate stem cell characteristics of gastric cancer cells
被引:24
作者:

Dai, Zhou-Tong
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Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Xiang, Yuan
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机构:
Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Med Lab, Wuhan 430014, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Duan, Yuan-yuan
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Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Wang, Jun
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Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Li, Jia Peng
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Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Zhang, Hui-Min
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Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Cheng, Chao
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Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastrointestinal Surg, Wuhan, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Wang, Qiong
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Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Zhang, Tong-Cun
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机构:
Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China
Tianjin Univ Sci & Technol, Coll Biotechnol, Key Lab Ind Fermentat Microbiol, Minist Educ & Tianjin, Tinajin 300457, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China

Liao, Xing-Hua
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机构:
Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China
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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Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore
Natl Univ Singapore, Yong Loo Lin Sch Med, Oncol Res Inst, Singapore 117595, Singapore Tokyo Med & Dent Univ, Dept Mol Oncol, Tokyo, Japan

Yuasa, Yasuhito
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Tokyo Med & Dent Univ, Dept Mol Oncol, Tokyo, Japan Tokyo Med & Dent Univ, Dept Mol Oncol, Tokyo, Japan