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miR-188-5p emerges as an oncomiRNA to promote gastric cancer cell proliferation and migration via upregulation of SALL4
被引:24
|作者:
Wang, Mei
[1
,2
]
Qiu, Rong
[1
,2
]
Gong, Zheng
[1
,2
]
Zhao, Xinxin
[1
,2
]
Wang, Tingting
[1
,2
]
Zhou, Lulu
[1
,2
]
Lu, Weiwei
[1
,2
]
Shen, Bo
[3
,4
]
Zhu, Wei
[1
,2
]
Xu, Wenrong
[1
,2
]
机构:
[1] Jiangsu Univ, Sch Med, Key Lab Med Sci, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[2] Jiangsu Univ, Sch Med, Lab Med Jiangsu Prov, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Affiliated Canc Hosp, Dept Oncol, Jiangsu Canc Hosp, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Inst Canc Res, Nanjing, Jiangsu, Peoples R China
基金:
中国国家自然科学基金;
中国博士后科学基金;
关键词:
gastric cancer;
migration;
miR-188-5p;
proliferation;
phosphatase and tensin homolog;
Sal-like protein 4;
TUMOR-SUPPRESSOR;
METASTASIS;
MIR-205;
GLIOMA;
D O I:
10.1002/jcb.28764
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:
MicroRNAs (miRNAs) play pivotal roles in modulating key biological processes in gastric cancer (GC). As a newly identified miRNA, the function and potential mechanism of miR-188-5p in GC has not been thoroughly elucidated. Here, quantitative real-time polymerase chain reaction detection showed abnormally higher expression of miR-188-5p in GC cells and tissues. Gain-of-function analysis in vitro showed that miR-188-5p promoted GC cell proliferation and migration, while loss-of-function studies showed the reverse. Targetscan has predicted that phosphatase and tensin homolog (PTEN) was a potential target gene of miR-188-5p. miR-188-5p suppressed PTEN messenger RNA and protein expression and activated downstream AKT/mTOR signaling in GC cells, but luciferase reporter analysis showed that PTEN was not regulated by miR-188-5p via the 3 ' untranslated region. Furthermore, we observed that miR-188-5p overexpression promoted Sal-like protein 4 (SALL4) protein expression, cellular nuclear translocation, and transcription. Knockdown of SALL4 eliminated the effect of miR-188-5p in GC cells as well as suppression of PTEN. Taken together, our results demonstrate that miR-188-5p promotes GC cell proliferation and migration while suppressing tumor suppressor gene PTEN expression via transcriptional upregulation of oncogene SALL4. We conclude that miR-188-5p acts as an oncomiRNA in GC and may be a promising therapeutic target for GC.
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页码:15027 / 15037
页数:11
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