Involvement of HIF-1 α-regulated miR-21, acting via the Akt/NF-κB pathway, in malignant transformation of HBE cells induced by cigarette smoke extract.

Involvement of HIF-1α-regulated miR-21, acting via the Akt/NF-κB pathway, in malignant transformation of HBE cells induced by cigarette smoke extract. Toxicol Lett. 2018 Feb 28;: Authors: Lu L, Xu H, Yang P, Xue J, Chen C, Sun Q, Yang Q, Lu J, Shi A, Liu Q Abstract Although the relationship between cigarette smoke and lung cancer has been widely studied, the molecular mechanism for cigarette smoke-induced lung cancer remains largely unclear. The present study investigated the roles of hypoxia-inducible factor (HIF)-1α and miR-21 in the malignant transformation of human bronchial epithelial (HBE) cells induced by cigarette smoke extract (CSE). In case of acute and chronic treatment of HBE cells, CSE increased the levels of HIF-1α, p-Akt, p-NF-κB, and miR-21 and decreased PTEN levels. The increased miR-21 levels induced by CSE were prevented by down-regulation of HIF-1α. Further, elevated miR-21 suppressed PTEN levels, which decreased the levels of p-Akt and p-NF-κB. However, those changes were attenuated in cells co-transfected with HIF-1α siRNA and an miR-21 mimic. Silencing of HIF-1α or NF-κB decreased colony formation and the invasion and migration capacities of CSE-transformed HBE cells; however, up-regulation of miR-21 reversed these effects. These results indicate that the oncogenic capacity of HIF-1α in regulation of miR-21-inhibited PTEN in a manner dependent on the Akt/NF-κB pathway, a process that is involved in ...
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research