Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.
Oncol Res. 2019 Sep 23;27(9):1007-1014. doi: 10.3727/096504018X15231148037228. Epub 2018 Apr 19.
Renal carcinoma greatly threatens human health, but the involved molecular mechanisms are far from complete understanding. As a master oncogene driving the initiation of many other cancers, ZBTB7 has not been established to be associated with renal cancer. Our data revealed that ZBTB7 is highly expressed in renal carcinoma specimens and cell lines, compared with normal cells. The silencing of ZBTB7 suppressed the proliferation and invasion of renal cancer cells. ZBTB7 overexpression rendered normal cells with higher proliferation rates and invasiveness. An animal study further confirmed the role of ZBTB7 in the growth of renal carcinoma. Moreover, miR-137 was identified to negatively regulate the expression of ZBTB7, and its abundance is inversely correlated with that of ZBTB7 in renal carcinoma specimens and cell lines. ZBTB7 overexpression may be induced by miR-137 downregulation. Interestingly, ZBTB7 can also suppress miR-137 expression by binding to its recognition site within the miR-137 promoter region. Taken together, we identified an autoregulatory loop consisting of ZBTB7 and miR-137 in gastric cancers, and targeting this pathway may be an effective strategy for renal carcinoma cancer therapy.
肾细胞癌极大地威胁着人类健康,但其中涉及的分子机制还远未完全阐明。作为一个驱动许多其他癌症发生的主要癌基因,ZBTB7 尚未被确定与肾细胞癌有关。我们的数据显示,与正常细胞相比,ZBTB7 在肾细胞癌标本和细胞系中高度表达。ZBTB7 的沉默抑制了肾癌细胞的增殖和侵袭。ZBTB7 的过表达使正常细胞具有更高的增殖率和侵袭性。动物研究进一步证实了 ZBTB7 在肾细胞癌生长中的作用。此外,miR-137 被鉴定为负调控 ZBTB7 的表达,其丰度与肾细胞癌标本和细胞系中 ZBTB7 的丰度呈负相关。ZBTB7 的过表达可能是由 miR-137 下调诱导的。有趣的是,ZBTB7 还可以通过结合 miR-137 启动子区域内的识别位点来抑制 miR-137 的表达。总之,我们在胃癌中鉴定了由 ZBTB7 和 miR-137 组成的自调控环路,靶向该途径可能是肾细胞癌治疗的有效策略。