CircMYBL1 suppressed acquired resistance to osimertinib in non-small-cell lung cancer

Yaji Li; Nan Wang; Yutang Huang; Shuai He; Meihua Bao; Chunjie Wen; Lanxiang Wu

doi:10.1016/j.cancergen.2024.04.001

CircMYBL1 suppressed acquired resistance to osimertinib in non-small-cell lung cancer

Cancer Genet. 2024 Apr 15:284-285:34-42. doi: 10.1016/j.cancergen.2024.04.001. Online ahead of print.

Authors

Yaji Li¹, Nan Wang¹, Yutang Huang¹, Shuai He², Meihua Bao³, Chunjie Wen⁴, Lanxiang Wu⁵

Affiliations

¹ Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
² Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing 400016, China.
³ Hunan key laboratory of the research and development of novel pharmaceutical preparations, Changsha Medical University, Changsha 410219, China; Academician Workstation, Changsha Medical University, Changsha 410219, China.
⁴ Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: wenchunj@cqmu.edu.cn.
⁵ Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: lxwu@cqmu.edu.cn.

PMID: 38626533
DOI: 10.1016/j.cancergen.2024.04.001

Abstract

Circular RNAs (circRNAs) play an important role in the development of acquired resistance to many anticancer drugs. We developed the Non-Small-Cell Lung Cancer (NSCLC) cell lines with acquired resistance to osimertinib, a third-generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and evaluated the different expression profiles of circRNAs in osimertinib-sensitive and -resistant NSCLC cell lines using RNA sequencing (RNA-Seq). The expression of selected differentially expressed circRNAs was verified using quantitative real-time PCR (qRT-PCR) in paired osimertinib-sensitive and -resistant NSCLC cell lines, and in plasma samples of osimertinib-sensitive and -resistant NSCLC patients. We found that circMYBL1(has_circ_0136924) was downregulated after acquired resistance to osimertinib, inhibiting circMYBL1 expression facilitated the proliferation, migration, and invasion in osimertinib-sensitive NSCLC cells. CircMYBL1 may be a novel molecular biomarker and therapeutic target for osimertinib-resistant NSCLC.

Keywords: Acquired resistance; Non-small-cell lung cancer; Osimertinib; RNA sequencing; circRNA.