Circular RNA SPECC1 promoted tumorigenesis and osimertinib resistance in lung adenocarcinoma via a circular RNA-microRNA network.

Abstract

Background: Tyrosine kinase inhibitors (TKIs) are the first-line therapy for patients with non-small cell lung cancer (NSCLC) with sensitized mutations in the epidermal growth factor receptor (EGFR). However, resistance to TKIs is a major clinical issue that affects the survival and prognosis of the patients, with the mechanisms underlying this resistance remaining elusive. Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules, which are generated from pre-messenger RNAs (mRNAs) through back splicing. The aim of this study was to investigate the role of cRNA SPECC1 in promoting resistance to TKIs in NSCLC and to explore its potential involvement in tumorigenesis and metastasis of lung adenocarcinoma (LUAD).

Methods: In this study, we identified differentially expressed genes through RNA sequencing from three tumor samples obtained from patients with poor postoperative TKI treatment outcomes. Validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and cell function experiments. We further constructed a competing endogenous RNA (ceRNA) network and performed Gene Ontology (GO) analysis to explore the underlying mechanisms of circRNA.

Results: SPECC1 circular RNA (circSPECC1) was found to be significantly upregulated in tumors as compared to adjacent tissues. Knockdown of circSPECC1 in NSCLC cell lines resulted in decreased proliferation, migration, and invasion. Additionally, apoptosis was increased in cell lines with TKI-sensitive EGFR mutations when treated with osimertinib.

Conclusions: circSPECC1 may promote TKI resistance and contribute to the tumorigenesis and metastasis of NSCLC. This study offers a novel perspective on TKI resistance research at the RNA level.