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ALKBH1 contributes to renal cell carcinoma progression by reducing N6-methyladenine of GPR137.

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Renal cell carcinoma (RCC) accounts for approximately 4% of all the adult malignancies with the high mortality worldwide. Although conventional chemotherapy and radiotherapy treatment has been applied for RCC in… Click to show full abstract

Renal cell carcinoma (RCC) accounts for approximately 4% of all the adult malignancies with the high mortality worldwide. Although conventional chemotherapy and radiotherapy treatment has been applied for RCC in clinic, the mortality rate of patients is increasing each year and patients with metastatic RCC are still suffering from poor prognosis. Thus, further investigation of the molecular mechanisms responsible for the development and progression of RCC is of particular importance. Here, we report that the expression of AlkB homolog 1 (ALKBH1) is up-regulated in RCC tissues, which is correlated with G protein-coupled receptor 137 (GPR137) expression. The elevated expression of ALKBH1 is associated with RCC cell malignant characteristics, including cell proliferation and movement (migration and invasion). Mechanistic investigation further reveals that ALKBH1 reduces m6 A levels of GPR137 mRNA in RCC cells, which up-regulates GPR137 mRNA levels, resulting in the increased GPR137 protein expression subsequently and the enhanced RCC cell biological actions consequently. In contrast, suppression of GPR137 effectively alleviates the ALKBH1-induced malignancies of RCC cells. Thus, our results indicate that ALKBH1-GPR137 axis might be used as a potential therapeutic target in RCC, contributing to finding new prognostic biomarkers for RCC at an early stage.

Keywords: cell; gpr137; cell carcinoma; renal cell; rcc; alkbh1

Journal Title: European journal of clinical investigation
Year Published: 2023

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