维生素D受体调控TRPV5/V6表达对肾细胞癌生物学行为的影响及其分子机制

Renal cell carcinoma(RCC) is a common urological cancer. Recently several lines of evidence showed that Vitamin D could decrease the RCC risk, increase survival and inhibit tumor growth, angiogenesis and metastasis. On the other hand, Vitamin D receptor (VDR)expression is lost or decreased during malignant transformation to RCC. Our team first reported that the expression of TRPV5/V6(Transient Receptor Potential Vanilloid subfamily 5 and 6) were decreased in RCC tissues, which were associated with VDR expression. Different expression were detected among the different RCC histopathological subtypes that arise from different origins. These findings likely suggested that altered VDR expression may be associated with RCC carcinogenesis via decreased TRPV5/6 expression. Moreover, it was found that the promoter core area of TRPV5/V6 contain the VDR identify series using bioinformatics analysis. Based on these evidences, we originally proposed that the VDR could regulate TRPV5/V6 transcription which might effect the development of RCC. In this research, we prepare to identify the mechanism of VDR to regulate TRPV5/V6 expression in RCC using EMSA,ChIP and RNAi,and then to investigate the possibility of biotherapy for RCC via VDR or/and TRPV5/V6.This study will provide a new theory to explain the molecular mechanism of RCC,and then to search a new biotherapy for RCC

多项流行病学研究证明维生素D可以降低人群肾癌的发病风险并且可以抑制肿瘤的生长和转移。本课题负责人前期研究首次在肾癌中发现维生素D受体（VDR）及TRPV5/V6表达降低且两者高度相关，但两者在肾癌发生中的关系和调控机制目前不清楚。本研究小组针对TRPV5/V6启动子核心区域运用生物信息学分析发现其中包含VDR转录因子识别序列，基于上述实验依据，我们首次提出VDR可调控TRPV5/V6转录影响肾癌发生的新假说。本课题拟首先通过EMSA、ChIP等实验技术获得VDR调控TRPV5/V6转录的证据，其次通过慢病毒介导的过表达及RNAi技术研究VDR调控TRPV5/V6对肾癌细胞恶性生物学行为的影响及其分子机制，最后通过构建肾癌裸鼠移植瘤模型探讨针对VDR或/和TRPV5/V6的肾癌生物治疗的可能性。本研究将为阐明肾癌的发病机制以及寻找新的肾癌生物治疗手段提供新的思路。