HMGA2 regulates lung cancer proliferation and metastasis

Xiaotian Gao, Ming Dai, Qinglan Li, Zhigang Wang, Yonglin Lu, Zeqing Song
Thoracic Cancer 2017, 8 (5): 501-510

BACKGROUND: This study aimed to explore the effects of HMGA2 on cell proliferation and metastases in lung cancer and its underlying mechanism.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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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