Abstract

Interleukin 6 (IL-6), a tumor promoting cytokine, has been largely implicated in the development of renal cell carcinoma (RCC). Hepatocyte cell adhesion molecule (hepaCAM) is a novel tumor suppressor, which is lost or down-regulated in many cancer types including RCC. In the present study, we intensively investigated the connection between IL-6 and hepaCAM in RCC. Our analysis of RCC tissues, adjacent tissues and paired serum samples from RCC patients revealed that IL-6 was elevated in patient serum and RCC tissue, whereas hepaCAM was completely lost or significantly down-regulated. Furthermore, we observed an association between IL-6 increase and hepaCAM decrease in RCC tissue samples. In the section of cytological researches, we found in RCC cell lines that IL-6 was a direct upstream regulator of hepaCAM, and that hepaCAM down-regulation was involved in IL-6-driven cell proliferation. We also demonstrated that IL-6-mediated promoter hypermethylation largely accounted for the hepaCAM loss in RCC, and it was STAT3-dependent. Additionally, our data showed that DNMT1 up-regulation induced by IL-6/STAT3 signaling was indispensable for IL-6-mediated hepaCAM loss in RCC cell lines ACHN and 769-P, while DNMT3b up-regulation was crucial for hepaCAM loss in A498. Our findings provide a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.