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miR‐665 promotes the progression of gastric adenocarcinoma via elevating FAK activation through targeting SOCS3 and is negatively regulated by lncRNA MEG3.
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- Author(s): Tang, Hailing; Long, Qianfa; Zhuang, Kun; Yan, Yuan; Han, Kun; Guo, Hanqing; Lu, Xiaolan
- Source:
Journal of Cellular Physiology; May2020, Vol. 235 Issue 5, p4709-4719, 11p
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- Abstract:
Studies have found that miR‐665 acted as a tumor suppressor or an oncogene in different malignancies. miR‐665 expression was elevated in gastric adenocarcinoma tissues; however, its role and mechanism in this disease are not fully clarified. The expression of miR‐665 and its target gene was detected in human gastric adenocarcinoma tissues and cells. Moreover, we analyzed the effects of miR‐665 on the proliferation, migration, and epithelial–mesenchymal transition (EMT) of gastric adenocarcinoma cells as well as tumor growth in vivo. The mechanisms of miR‐665 in gastric adenocarcinoma were investigated by using molecular biology techniques. We found miR‐665 was upregulated and suppressor of cytokine signaling 3 (SOCS3) was downregulated in gastric adenocarcinoma tissues and cells. Elevated miR‐665 was positively correlated with tumor size, lymph node metastasis, invasion depth, TNM stage, and poor differentiation in gastric adenocarcinoma patients. Overexpression of miR‐665 promoted, whereas knockdown of miR‐665 suppressed the proliferation, migration, and EMT of gastric adenocarcinoma cells. Furthermore, we demonstrated that miR‐665 functioned through targeting SOCS3, followed by activation of the FAK/Src signaling pathway in gastric adenocarcinoma cells. miR‐665 antagomir inhibited tumor growth as well as the activation of the FAK/Src pathway but increased SOCS3 expression in nude mice. In addition, miR‐665 expression was negatively regulated by long noncoding RNA maternally expressed gene 3 (MEG3). In conclusion, miR‐665 acted as an oncogene in gastric adenocarcinoma by inhibiting SOCS3 followed by activation of the FAK/Src pathway and it was negatively modulated by MEG3. miR‐665 may be a promising therapeutic target for the treatment of gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]
- Abstract:
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