Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2.
Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2.
复制标题
睾丸核受体4通过Bcl-2调节膀胱癌的增殖和凋亡
DOI：
10.3389/fmolb.2021.670409
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发表时间：
2021
影响因子：
5
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Wang H;Luo W;Wang X;Xue D;Ren L;Xu L;Ge G;Xia L;Yu S;Wang M;Zhou Z;Li G;Wu H
睾丸核受体4（TR 4）是核激素受体家族的成员，作为配体激活的转录因子，在许多生物学过程中发挥作用，如发育，细胞分化和稳态。最近的研究表明，TR 4在前列腺癌，肾细胞癌和肝细胞癌中起着重要作用;然而，其与膀胱癌（BC）的潜在联系仍然未知。这项研究发现，膀胱癌与正常组织相比，TR 4的表达更高。过表达TR 4促进膀胱癌细胞增殖，用TR 4-siRNA敲减TR 4抑制膀胱癌细胞增殖。机制研究表明，TR 4通过改变Bcl-2的表达来调节膀胱癌细胞的凋亡。此外，敲低Bcl-2逆转TR 4诱导的BC增殖。在体内，我们还证实了TR 4敲除小鼠（TR 4 +/−）比致癌化学物质诱导的野生型小鼠（TR 4 +/+）表现出更慢的膀胱癌生长。此外，TR 4 +/−小鼠的组织病理学分级低于对照组。总之，这些结果表明TR 4在膀胱癌增殖中起关键作用，靶向TR 4可能是膀胱癌治疗的潜在策略。
Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/−) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/− mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.