E2F1-induced long non-coding RNA MCF2L-AS1 modulates Cyclin D1 mRNA stability through ELAVL1 to induce Gefitinib resistance in non-small cell lung cancer

  • Kui Zhong Shan Department of Pulmonary Nodule Center, The Second People’s Hospital of Kunshan, Suzhou, China https://orcid.org/0000-0001-9967-8644
  • Su Fang Yang Department of Pulmonary Nodule Center, The Second People’s Hospital of Kunshan, Suzhou, China
  • Yu Jiang Deng Department of Pulmonary Nodule Center, The Second People’s Hospital of Kunshan, Suzhou, China
  • Pei Yu Yue Department of Pulmonary Nodule Center, The Second People’s Hospital of Kunshan, Suzhou, China
  • Zhi Quan Du Department of Pulmonary Nodule Center, The Second People’s Hospital of Kunshan, Suzhou, China
DOI: https://doi.org/10.18388/abp.2020_6118

Abstract

Purpose: Gefitinib is a widely used therapeutic drug for non-small cell lung cancer (NSCLC), and its acquired resistance has become one of the barriers to the successful use of the drugs to treat NSCLC patients. Long non-coding RNA (lncRNA) has an essential role in developing cancer drug resistance. Hence, this study aimed to investigate the effect and modulatory mechanisms of lncRNA MCF2L-AS1 in Gefitinib resistance in NSCLC. Methods: IBEAS-2B and A549 cells and human NSCLC tissues were used. A549/GR cell line was constructed by continuous exposure to Gefitinib. Cell viability, apoptosis, migration, colony formation, and protein expression studies were done in transfected cells. Interactions of MCF2L-AS1, ELAVL1, and Cyclin D1 (CCND1 was also investigated. Results: In patients with Gefitinib-resistant NSCLC, MCF2L-AS1 and CCND1 were both up-regulated. Knockdown of MCF2L-AS1 reduced Gefitinib-resistant NSCLC cell progression, indicating that inhibition of MCF2L-AS1 restrained Gefitinib-resistant NSCLC. Mechanically, MCF2L-AS1 enhanced CCND1 mRNA stability via combining with ELAVL1, thereby elevating the resistance of NSCLC cells to Gefitinib. Moreover, E2F1 could transcriptionally up-regulate MCF2L-AS1. Conclusion: The results manifest that lncRNA MCF2L-AS1, as an oncogene of NSCLC, controls CCDN1 via ELAVL1 to drive the growth of NSCLC cells and Gefitinib resistance.

Published
2022-10-18
Issue
Vol. 69 No. 4 (2022)
Section
Articles

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