Open AccessOccludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4
Author(s) -
Yang Fan,
Liu XueQi,
He JianZhong,
Xian ShiPing,
Yang PengFei,
Mai ZhiYing,
Li Miao,
Liu Ye,
Zhang XingDing
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17257
Subject(s) - angiogenesis , stat3 , cancer research , stat4 , biology , stat protein , transcription factor , occludin , interleukin 8 , neovascularization , downregulation and upregulation , signal transduction , stat , immunology , tight junction , microbiology and biotechnology , gene , cytokine , genetics
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.