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Research Paper|Volume 11, Issue 7|pp 2138—2150

MiR-204 reduces cisplatin resistance in non-small cell lung cancer through suppression of the caveolin-1/AKT/Bad pathway

Gang Huang1, Tianzheng Lou2, Jiongwei Pan3, Zaiting Ye4, Zhangyong Yin3, Lu Li3, Wei Cheng5,6, Zhuo Cao3
  • 1Department of Traditional Chinese Medicine, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui 323000, China
  • 2Department of Intensive Care Unit, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui 323000, China
  • 3Department of Respiratory, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui 323000, China
  • 4Department of Radiology, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui 323000, China
  • 5Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou 221002, China
  • 6, The People's Hospital of Kizilsu Kirghiz Autonomous Prefecture, Xinjiang 845350, China

* * Equal contribution

Received: January 26, 2019Accepted: April 3, 2019Published: April 12, 2019
https://doi.org/10.18632/aging.101907

Copyright: Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Non-small cell lung cancer (NSCLC) is the most common and lethal human malignant tumor worldwide. Platinum-based chemotherapy is still the mainstay of treatment for NSCLC. However, long-term chemotherapy usually induces serious drug resistance in NSCLC cells. Accordingly, treatment strategies that reverse the resistance of NSCLC cells against platinum-based drugs may have considerable clinical value. In the present study, we observed significant upregulation of CAV-1 expression and a significant decrease of miR-204 expression in cisplatin-resistant A549 (CR-A549) and cisplatin-resistant PC9 (CR-PC9) cells compared to their parental A549 and PC9 cells. Furthermore, we demonstrated that the downregulation of miR-204 expression was responsible for CAV-1 overexpression in these cisplatin-resistant NSCLC cells. We then found that enforced expression of miR-204 can resensitize CR-A549 and CR-PC9 cells to cisplatin-induced mitochondrial apoptosis through suppression of the caveolin-1/AKT/Bad pathway. We demonstrated that dysregulation of miR-204/caveolin-1 axis is an important mechanism for NSCLC cells to develop the chemoresistance.