Regulating POLR3G by MicroRNA-26a-5p as a promising therapeutic target of lung cancer stemness and chemosensitivity

초록

Cancer stem cells (CSCs) identified in lung cancer exhibit resistance to chemotherapy, radiotherapy, and targeted therapy. Therefore, a technology for controlling CSCs is needed to overcome such resistance to cancer therapy. Various evidences about the association between epithelial-mesenchymal transition related transcriptomic alteration and acquisition of CSC phenotype have been proposed recently. Down-regulated miR-26a-5p is closely related to mesenchymal-like lung cancer cell lines. These findings suggest that miR-26a-5p might be involved in lung cancer stemness. RNA polymerase III subunit G (POLR3G) was selected as a candidate target of miR-26a-5p related to cancer stemness. It was found that miR-26a-5p directly regulates the expression of POLR3G.Overexpression of miR-26a-5p induced a marked reduction of colony formation and sphere formation. Co-treatment of miR-26a-5p and paclitaxel decreased cell growth, suggesting that miR-26a-5p might play a role as a chemotherapy sensitizer. In the cancer genome atlas data, high miR-26a-5p and low POLR3G expression were also related to higher survival rate of patients with lung adenocarcinoma. These results suggest that miR-26a-5p can suppress lung cancer stemness and make cancer cell become sensitive to chemotherapy. This finding provides a novel insight into a potential lung cancer treatment by regulating stemness.

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