Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4.
Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4.
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DOI：
10.1111/jcmm.17257
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发表时间：
2022-04
影响因子：
5.3
通讯作者：
Zhang XD
中科院分区：
文献类型：
--
作者：
Yang F;Liu XQ;He JZ;Xian SP;Yang PF;Mai ZY;Li M;Liu Y;Zhang XD
膀胱癌(BLCA)是常见的泌尿生殖系肿瘤，肿瘤血管生成是其发生发展不可缺少的环节。然而，BLCA中肿瘤血管生成的深层机制仍不清楚。最近的研究表明，紧密连接蛋白家族成员occludin(OCLN)在BLCA组织中高水平表达，与预后不良相关。OCLN的下调抑制了BLCA细胞和小鼠移植瘤中的肿瘤血管生成，而OCLN的过度表达则起到相反的作用。机制方面，RT-qPCR分析和Western blotting结果表明，OCLN可促进BLCA血管生成，增加IL-8和转录活化因子3(STAT3)的水平。RNA测序分析和双荧光素酶报告分析表明，OCLN通过转录因子STAT4调节IL8的转录活性。总之，我们的结果为OCLN提供了新的视角，因为该蛋白通过STAT4激活IL8/STAT3途径参与BLCA血管生成的发展，并可能作为一个新的和独特的治疗靶点。
Bladder cancer (BLCA) is a common genitourinary cancer in patients, and tumour angiogenesis is indispensable for its occurrence and development. However, the indepth mechanism of tumour angiogenesis in BLCA remains elusive. According to recent studies, the tight junction protein family member occludin (OCLN) is expressed at high levels in BLCA tissues and correlates with a poor prognosis. Downregulation of OCLN inhibits tumour angiogenesis in BLCA cells and murine xenografts, whereas OCLN overexpression exerts the opposite effect. Mechanistically, the RT‐qPCR analysis and Western blotting results showed that OCLN increased interleukin‐8 (IL8) and p‐signal transducer and activator of transcription 3 (STAT3) levels to promote BLCA angiogenesis. RNA sequencing analysis and dual‐luciferase reporter assays indicated that OCLN regulated IL8 transcriptional activity via the transcription factor STAT4. In summary, our results provide new perspectives on OCLN, as this protein participates in the development of BLCA angiogenesis by activating the IL8/STAT3 pathway via STAT4 and may serve as a novel and unique therapeutic target.
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