Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/β-catenin signaling pathway in lung adenocarcinoma

外泌体介导的 miR-1260b 转移通过 Wnt/β-catenin 信号通路促进肺腺癌细胞侵袭

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作者:Yang Xia, Ke Wei, Liu-Qing Hu, Cun-Rong Zhou, Zhi-Bin Lu, Gen-Sheng Zhan, Xiang-Long Pan, Chun-Feng Pan, Jun Wang, Wei Wen, Jing Xu, Zhi-Cheng He, Chen-Jun Huang, Liang Chen

Abstract

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/β-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.

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