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MicroRNA-145 promotes esophageal cancer cells proliferation and metastasis by targeting SMAD5.

Scand. J. Gastroenterol.2018 Jun - Jul ;53(7):769-776. doi:10.1080/00365521.2018.1476913. Epub 2018 May 31
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摘要


OBJECTIVE:To clarify the relative expression and molecular function of microRNA (miR)-145 in esophageal cancer and understand its mechanistic involvement in this disease. MATERIAL AND METHODS:The relative expression of miR-145 in clinical samples was analyzed using the public GSE43732 dataset. The prognostic analysis with respect to miR-145 expression was performed with Kaplan-Meier plot. Cell viability was measured by MTT assay and the anchorage-independent growth was evaluated by soft agar assay. The migration and invasion of esophageal cancer cells were measured using transwell chamber. The regulatory effect of miR-145 on SMAD5 was determined by dual-luciferase reporter assay. The endogenous SMAD5 protein was measured by Western blot. RESULTS:We demonstrated high expression of miR-145 associated with late stage and unfavorable prognosis of esophageal cancer. Ectopic expression of miR-145 mimic significantly stimulated cell proliferation and anchorage-independent growth. Furthermore, high level of miR-145 significantly promoted both migration and invasion in vitro. Notably, we identified SMAD5 as direct target of miR-145, the suppressed expression of which consequently led to increased cell proliferation and migration/invasion. CONCLUSION:Our study uncovered the crucial role of miR-145/SMAD5 in esophageal cancer and highlighted its target potential for diagnostic and therapeutic purpose.

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