Abstract:
Objective To identify the micro-RNAs related to the regulation of CD40 signaling, and explore their roles in regulating the CD40 signaling in renal cell carcinoma, which may provide new and effective potential targets for the diagnosis and treatment of renal cell carcinoma in the future.
Methods The micro-RNA expression profiles of renal cell carcinoma and adjacent control cells were analyzed by gene chip. Bioinformatics predicted the micro-RNA that may regulate CD40, and its expression was verified by RT-PCR. Micro-RNA inhibitors and mimics were transfected in vitro to study their effects on the expression of CD40 and CD40L, and their effects on the secretion of cytokines and cell proliferation of renal cell carcinoma cells.
Results The expression of miR-145 was significantly reduced in the renal cell carcinoma group(P < 0.01). After transfection with miR-145 inhibitor, CD40 expression was significantly increased in renal cell carcinoma cells, and there was no statistical difference in CD40L expression. After the transfection of miR-145 mimics, CD40 expression was significantly reduced in renal cell carcinoma cells, and there was no statistical difference in CD40L expression. After functionally elevating the expression of miR-145, the expression of tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ) decreased significantly, and tumor cell proliferation slowed. After functionally decreasing the expression of miR-145, the expression of TNF-α and IFN-γ increased significantly, and tumor cell proliferation accelerated(P < 0.01). After antagonizing the expression of CD40 and elevating the expression of miR-145, TNF-α, and IFN-γ were down regulated, but there was no statistical difference.
Conclusion miR-145 is significantly reduced in renal cell carcinoma cells, and by regulating the expression of CD40, it further regulates cytokine secretion and cell proliferation and promotes the occurrence and development of tumors.