miR-519d-3p suppresses tumorigenicity and metastasis by inhibiting Bcl-w and HIF-1α in NSCLC

• Published in: Molecular therapy. Oncolytics 2021-09, Vol.22, p.368-379
• Main Authors: Choi, Jae Yeon, Seok, Hyun Jeong, Kim, Rae-Kwon, Choi, Mi Young, Lee, Su-Jae, Bae, In Hwa
• Format: Article
• Language: English
• Subjects: Bcl-w; HIF-1α; hypoxia; miR-519d-3p; NSCLC; Original; solid tumor
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2021.06.015

Bcl-w, a member of the Bcl-2 family, is highly expressed in various solid tumor, including lung cancer, suggesting that it is involved in cancer cell survival and carcinogenesis. Solid cancer-induced hypoxia has been reported to increase angiogenesis, growth factor, gene instability, invasion, and metastasis. Despite many studies on the treatment of non-small cell lung cancer (NSCLC) with a high incidence rate, the survival rate of patients has not improved because the cancer cells acquired resistance to treatment. This study investigated the correlation between Bcl-w expression and hypoxia in tumor malignancy of NSCLC. Meanwhile, microRNAs (miRNAs) are involved in a variety of key signaling mechanisms associated with hypoxia. Therefore, we discovered miR-519d-3p, which inhibits the expression of Bcl-w and hypoxia-inducing factor (HIF)-1α, and found that it reduces hypoxia-induced tumorigenesis. Spearman’s correlation analysis showed that the expression levels of miR-519d-3p and Bcl-w/HIF-1α were negatively correlated, respectively. This showed that miR-519d-3p can be used as a diagnostic biomarker and target therapy for NSCLC. [Display omitted] This study investigated the correlation between Bcl-w overexpressed in solid cancer NSCLC and HIF-1α, a hypoxia-related factor, and discovered miR-519d-3p, which inhibited these two factors to suppress hypoxia-induced malignancy. These results showed that miR-519d-3p could be used as a biomarker of diagnosis and targeted therapy for NSCLC.