HMGA2 regulates lung cancer proliferation and metastasis.

HMGA2 regulates lung cancer proliferation and metastasis.
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DOI:
10.1111/1759-7714.12476
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发表时间:
2017-09
期刊:
影响因子:
2.9
通讯作者:
Song Z
Song Z
中科院分区:
医学3区
文献类型:
--
作者:
Gao X;Dai M;Li Q;Wang Z;Lu Y;Song Z

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本研究旨在探讨HMGA2对肺癌细胞增殖和转移的影响及其机制。基于公共数据库的数据分析肺癌组织中HMGA2的表达及其与总生存率的关系。通过体外功能丧失和功能获得实验验证了HMGA2的作用。通过real - time - PCR、Western blotting和荧光素酶报告基因检测验证microRNA‐195 (miR‐195)对HMGA2的调控作用。HMGA2在肺腺癌患者中上调并与总生存率降低相关。HMGA2敲低抑制了H1299细胞的增殖和运动,而HMGA2异位表达在A549细胞中增加了细胞的增殖和迁移。HMGA2通过caspase 3/9和Bcl‐2影响细胞凋亡,并通过靶向Twist‐1调控上皮向间质转化。此外,miR - 195被发现直接靶向HMGA2信使RNA的3 '非翻译区并抑制其在肺癌中的表达。该研究表明,miR - 195调控的HMGA2在肺癌的增殖、转移和上皮-间质转化中发挥重要作用。HMGA2可能作为一种生物标志物和潜在的肺癌治疗靶点。
This study aimed to explore the effects of HMGA2 on cell proliferation and metastases in lung cancer and its underlying mechanism. HMGA2 expression in lung cancer tissues and its association with overall survival were analyzed based on data from a public database. The roles of HMGA2 were validated via loss‐of‐function and gain‐of‐function experiments in vitro. HMGA2 regulation by microRNA‐195 (miR‐195) was validated by real time‐PCR, Western blotting, and luciferase reporter assays. HMGA2 was upregulated and associated with reduced overall survival in patients with lung adenocarcinoma. HMGA2 knockdown suppressed the proliferation and motility of H1299 cells, while HMGA2 ectopic expression in A549 cells increased cell proliferation and migration. HMGA2 affected cell apoptosis through caspase 3/9 and Bcl‐2, and regulated epithelial‐to‐mesenchymal transition by targeting Twist 1. Moreover, miR‐195 was found to directly target the 3′ untranslated region of HMGA2 messenger RNA and suppress its expression in lung cancer. This study demonstrated that HMGA2, regulated by miR‐195, played important roles in proliferation, metastases, and epithelial‐to‐mesenchymal transition in lung cancer. HMGA2 might serve as a biomarker and potential therapeutic target for lung cancer treatment.
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