Lung cancer, as the most commonly diagnosed malignancy, still accounts for the leading cause of cancer-related deaths worldwide. The high rate of mortality and tumor recurrence has prompted clinicians and scientists to urgently explore new targets for improved treatment. Previous studies have indicated a potential role of the androgen receptor (AR) in the progression of non-small cell lung cancer (NSCLC). However, the precise mechanisms underlying this association, particularly its relation to TPD52-mediated cell invasion and cisplatin (DDP) response, have not been fully elucidated. Therefore, further investigation is necessary to gain a better understanding of these mechanisms and their potential implications for lung cancer treatment. In this study, we discovered that AR can suppress NSCLC cell invasion and increase cisplatin response by downregulating the expression of circular RNA (circRNA), specifically circ-SLCO1B7. This suppression is achieved through the direct binding of AR to the 5' promoter region of the host gene SLCO1B7. The decreased expression of circ-SLCO1B7, mediated by AR, released miR-139-5p back to the RISC (RNA induced silencing complex), where it bonds to the 3' untranslated region (3'UTR) of Tumor Protein D52 (TPD52) messenger RNA, resulting in TPD52 reduction. The in vivo data also validated the functional contribution of AR/circ-SLCO1B7/miR-139-5p/TPD52 axis to lung cancer progression. Furthermore, analysis of human NSCLC databases and clinical specimens confirmed the association of the AR/circ-SLCO1B7/miR-139-5p/TPD52 signaling pathway with NSCLC progression. Collectively, the results from our study suggest that AR can suppress lung cancer cell invasion and increase DDP response by modulating the circ-SLCO1B7/miR-139-5p/TPD52 signaling pathway. Targeting this novel signaling pathway may be a new therapeutic strategy to effectively constrain NSCLC development.
Keywords: TPD52; androgen receptor; cisplatin response; invasion; lung cancer.
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