Abstract 759: microRNA 26a-5p inhibited stemness and enhanced the chemosensitivity of non-small cell lung cancer

Abstract

Only a subpopulation of cells which have the ability to regulate self-renewal and differentiation of cancer cells, are able to tumorigenic capacity. This subpopulation of cells is called cancer stem cells (CSC). Cancer stem cells are also identified in lung cancer and exhibits resistance to chemotherapy, radiotherapy and targeted therapy. Therefore, the technology to control CSCs is a good strategy to overcome resistance to cancer therapy. Epithelial-mesenchymal transition (EMT) has been linked with the generation of cancer stem cells (CSCs). Recent evidence proposes that EMT-related transcriptomic alterations correlate with the acquisition of CSC phenotype. In previous study, we investigated the miRNA profiles of mesenchymal-like lung cancer cell lines to evaluate the relationship beween EMT and miRNA in non-small cell lung cancer (NSCLC). miR-26a-5p is down-regulated in mesenchymal like lung cancer cell lines. These findings suggested miR-26a-5p may be involved in cancer stemness of lung cancer cells. To test that miR-26a-5p has a role in stemness of lung cancer, we performed colony formation assay, sphere formation assay and fluorescence activated cell sorting. RNA polymerase III subunit G (POLR3G) was selected as a candidate target of miR-26a-5p related to cancer stemness. To verify that miR-26a-5p regulates POLR3G, we performed qRT-PCR, western blot and luciferase assays. Cell proliferation assay was performed to evaluate miR-26a-5p’s role of chemosensitizer. The overexpression of miR-26a-5p induced a marked reduction of the colony formation and sphere formation in non-small lung cancer cell lines. Overexpression of miR-26a-5p lead to reduction of CD133+ cells. Co-treatment with miR-26-5p and Paclitaxel treatment showed a significant reduction of growth. miR-26a-5p regulated the expression of POLR3G at the mRNA and protein levels. These data demonstrate for the first time that miR-26a-5p suppresses lung cancer stemness by repressing POLR3G expression. This provides new insight into a potential approach for the treatment of lung cancer by regulating cancer stemness. Citation Format: Jiwoong Son, Sun Jung Kwon, In Beom Jeong, Ji Hye Kim. microRNA 26a-5p inhibited stemness and enhanced the chemosensitivity of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 759.