MiR-192/NKRF axis confers lung cancer cell chemoresistance to cisplatin via the NF-κB pathway.

Abstract

BACKGROUND:

Chemoresistance influences the therapeutic effect of cisplatin and remains a major obstacle to its clinical use. MicroRNAs are associated with drug resistance of various tumors. However, the association between microRNAs and cisplatin in lung cancer remains largely unclear.

METHODS:

MicroRNA expression profile was identified by microRNA microarray between the lung cancer cisplatin-sensitive cell line A549 (A549) and cisplatin-resistant cell line A549/DDP (A549/DDP) and confirmed by quantitative real-time-PCR (qRT-PCR). In vitro loss- and gain-of-function studies were performed to reveal the biological function of miR-192 and related mechanism of the microRNA-192/NKRF axis in lung cancer cell cisplatin resistance.

RESULTS:

Increased miR-192 expression was detected in A549/DDP cells compared to A549. High miR-192 expression significantly suppressed apoptosis, enhanced proliferation, and conferred resistance to cisplatin in lung cancer cells. NF-κB repressing factor (NKRF), which is involved in the regulation of the NF-κB signaling pathway, was identified as a direct target of miR-192. Overexpression of miR-192 significantly increased the nuclear protein amount and transcriptional activation of NF-κB and expression of cIAP1, cIAP2, Bcl-xl and XIAP, whereas decreased miR-192 expression did the opposite. Inhibition of the NF-κB signal pathway by curcumin reversed the effect of upregulation of miR-192 on proliferation, apoptosis and cisplatin-resistance in lung cancer cells. These results indicated that miR-192/ NKRF axis enhances the cisplatin resistance of lung cancer cells through activating the NF-κB pathway in vitro.

CONCLUSIONS:

MiR-192 plays a crucial role in cisplatin-resistance of lung cancer cells. Thus, MiR-192 may represent a therapeutic target for overcoming resistance to cisplatin-based chemotherapy in lung cancer.

• Authors: Yang Li, Lingling Zu, Heng Wu, Fang Zhang, Yaguang Fan, Hongli Pan, Xinxin Du, Fengjie Guo, Qinghua Zhou
• Journal: Thoracic cancer (Thorac Cancer) Vol. 13 Issue 3 Pg. 430-441 (02 2022) ISSN: 1759-7714 [Electronic] Singapore
• PMID: 34953057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Chemical References

• Antineoplastic Agents
• MIRN192 microRNA, human
• MicroRNAs
• NF-kappa B
• Cisplatin

Topics

• A549 Cells
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Cell Proliferation
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• MicroRNAs (genetics, metabolism)
• NF-kappa B (genetics, metabolism)