LncRNA TSLNC8 synergizes with EGFR inhibitor osimertinib to inhibit lung cancer tumorigenesis by blocking the EGFR-STAT3 pathway

Abstract

ABSTRACT The roles of lncRNA TSLNC8 and its synergetic effects with osimertinib remain unknown in lung cancer. qRT-PCR or western blotting was performed to determine the expression levels of TSLNC8, EGFR and STAT3. Colony formation and MTT assays were used to evaluate cell proliferation. Transwell and wound healing assays were performed to assess migration and invasion abilities. Flow cytometry with Annexin V/PI staining was used to detect changes in cell apoptosis. Nude mice subcutaneous tumor model was constructed and used for validating the effects of TSLNC8 and osimertinib in vivo. Expression of TSLNC8 was down-regulated in clinical lung cancer tissues and cell lines. TSLNC8 overexpression or osimertinib administration led to promotion of apoptosis and inhibition of cell proliferation, migration and invasion, as well as deactivation of the EGFR-STAT3 pathway, whereas TSLNC8 knockdown had opposite effects. Moreover, the above effects of osimertinib were remarkably enhanced by TSLNC8 overexpression and inhibited by TSLNC8 knockdown, respectively. Meanwhile, the effects of TSLNC8 overexpression were reversed by STAT3 activation or EGFR overexpression. In the animal model, combination of TSLNC8 overexpression and osimertinib administration resulted in efficient suppression of tumor growth. In this study, we revealed a TSLNC8-EGFR-STAT3 signaling axis in lung cancer, and TSLNC8 overexpression significantly enhanced the anti-tumor effects of osimertinib via inhibiting EGFR-STAT3 signaling.