Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal malignancy. Methyltransferase like 13 (METTL13) functions as an oncogene in most of human cancers, but its function and mechanism in ccRCC remain unreported. Methods: qRT-PCR, western blot and immunohistochemistry were used to detect METTL13’s expressions in tissues. The effects of METTL13 on ccRCC cells’ growth and metastasis were determined by both functional experiments and animal experiments. Weighted gene co-expression network analysis (WGCNA) was performed to annotate METTL13’s functions and co-immunoprecipitation (co-IP) was used to determine the interaction between two proteins. Results: METTL13 was lowly expressed in ccRCC tissues compared to normal kidney tissues and its low expression predicted poor prognosis for ccRCC patients. In vitro study indicated METTL13’s inhibition on ccRCC cells’ proliferation, viability, migratory ability and invasiveness as well as epithelial-mesenchymal transition (EMT). Bioinformatic analyses showed various biological functions and pathways METTL13 was involved in. In ccRCC cells, we observed that METTL13 could negatively regulate PI3K/AKT/mTOR/HIF-1α pathway and that it combined to c-Myc and inhibited c-Myc expression. In vivo experiment confirmed that METTL13 inhibited ccRCC cell growth and metastasis. Conclusions: In general, our finding suggests that associated with favorable prognosis of ccRCC patients, METTL13 can inhibit growth and metastasis of ccRCC cells with multiple potential molecular mechanisms. Therefore, it’s likely for METTL13 to serve as a new diagnostic and therapeutic target for ccRCC in the future.