Lung cancer is the main cause of cancer-related death, and the proportion of non-small cell lung cancer (NSCLC) on lung cancer is 85%, while more than 80% lung cancer patients are diagnosed with chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the potential mechanism of COPD induced NSCLC. Luciferase assay and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to study the regulatory relationship between P53 and microRNA-675 (miR-675). Real-time PCR, Western-blot analysis, and MTT assay were performed to explore the impact of H19 and miR-675 in the signaling pathway involved in COPD induced NSCLC. In NSCLC patients with COPD, H19 and miR-675 levels were strikingly upregulated while P53 level was significantly downregulated. P53 was identified as a target gene of miR-675, and H19 remarkably upregulated miR-675, while H19 siRNA notably inhibited miR-675. In addition, miR-675 and H19 dramatically suppressed the expression of P53 and Bax while inducing the expression of Bcl-2. Finally, H19 and miR-675 induced proliferation of A549 and MRC-5 cells. These finding indicated that COPD (hypoxia)-induced H19 promoted expression of miR-675 associated with NSCLC though target apoptosis-related protein P53, BAX, and Bcl-2.
Keywords: H19; TP53; apoptosis; hypoxia; lncRNA; microRNA-675; non-small cell lung cancer; oncogenesis; proliferation.
© 2019 Wiley Periodicals, Inc.