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

Jae Yeon Choi; Hyun Jeong Seok; Rae-Kwon Kim; Mi Young Choi; Su-Jae Lee; In Hwa Bae

doi:10.1016/j.omto.2021.06.015

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

Mol Ther Oncolytics. 2021 Jul 10:22:368-379. doi: 10.1016/j.omto.2021.06.015. eCollection 2021 Sep 24.

Authors

Jae Yeon Choi¹, Hyun Jeong Seok¹, Rae-Kwon Kim², Mi Young Choi², Su-Jae Lee², In Hwa Bae¹

Affiliations

¹ Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
² Department of Life Science, Hanyang University, Seoul, Republic of Korea.

Abstract

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.

Keywords: Bcl-w; HIF-1α; NSCLC; hypoxia; miR-519d-3p; solid tumor.