An oncogenic role of lncRNA SNHG1 promotes ATG7 expression and autophagy involving tumor progression and sunitinib resistance of Renal Cell Carcinoma

Abstract

AbstractRenal cell carcinoma (RCC) is a malignant tumor with high incidence in adult kidney. Long non-coding RNAs (lncRNAs) have recently been recognized as important regulators in the development of RCC. However, whether lncRNA SNHG1 is associated with RCC progression remains to be elucidated. Here, the role of SNHG1 in RCC autophagy and sunitinib resistance was evaluated. Expression of SNHG1 in RCC tissues and cells was assessed using RT-qPCR. Western blot was utilized to measure the levels of autophagy-related molecules and ATG7. RNA pull-down and RIP assays were performed to confirm the molecular axis between SNHG1/PTBP1/ATG7. Cell proliferation, migration, invasion and apoptosis were analyzed by CCK-8, EdU, transwell and flow cytometry, respectively. The subcellular localization of SNHG1 was determined by an intracellular fractionation assay. The fluorescence intensity of GFP-LC3 autophagosome in RCC cells was detected. IHC staining was performed to test ATG7 expression in tumor tissues from nude mice. Here, a positive correlation of upregulated SNHG1 with poor prognosis of RCC patients was observed in RCC tissues and cells. SNHG1 knockdown suppressed tumor growth and reversed sunitinib resistance and autophagy of RCC cells. Additionally, SNHG1 was found to directly bind to PTBP1, thereby positively regulating ATG7 expression. Furthermore, we verified that SNHG1 mediated the malignant behavior of RCC cells through the PTBP1/ATG7 axis. To sum up, SNHG1 regulates RCC cell autophagy and sunitinib resistance through the PTBP1/ATG7 axis, which highlights a promising therapeutic target for RCC treatment.