Affiliation:
1. National Clinical Research Center for Child Health of the Children's Hospital Zhejiang University School of Medicine Hangzhou 310052 China
2. Department of Urology Third Affiliated Hospital of the Second Military Medical University Shanghai 201805 China
3. The Department of Obstetrics and Gynecology Ruijin Hospital, Shanghai Jiaotong University School of Medicine 197 Ruijin 2nd Road, Huangpu District Shanghai 200025 China
4. Department of Urology Xinhua Hospital, Shanghai Jiaotong University, School of Medicine 1665 Kongjiang Road Shanghai 200092 China
Abstract
AbstractBackgroundRenal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies with 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.MethodsTotal of 10 pairs of RCC tissues and adjacent nontumor tissues were collected for examination of ALKBH1 and GPR137 expression. The correlations between ALKBH1 and GPR137 expression in RCC patient were assessed by GEPIA online tool and were analyzed using auto best cutoff. The human RCC cell lines Caki‐1, 786‐O, ACHN, Osrc2, A498, and 769‐P, were used for mechanistic investigation.ResultsHere, we report that the expression of AlkB homologue 1 (ALKBH1) is upregulated 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 m6A levels of GPR137 mRNA in RCC cells, which upregulates GPR137 mRNA levels, resulting in the increased GPR137 protein expression subsequently and the enhanced RCC cell biological actions consequently. In contrast, the suppression of GPR137 effectively alleviates the ALKBH1‐induced malignancies of RCC cells.ConclusionOur 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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Shanghai
Subject
Clinical Biochemistry,Biochemistry,General Medicine
Cited by
7 articles.
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