Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4.
Fan YangXue-Qi LiuJian-Zhong HeShi-Ping XianPeng-Fei YangZhi-Ying MaiMiao LiYe LiuXing-Ding ZhangPublished in: Journal of cellular and molecular medicine (2022)
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.
Keyphrases
- cell proliferation
- endothelial cells
- transcription factor
- vascular endothelial growth factor
- poor prognosis
- wound healing
- gene expression
- long non coding rna
- end stage renal disease
- induced apoptosis
- ejection fraction
- signaling pathway
- newly diagnosed
- risk assessment
- prognostic factors
- south africa
- crispr cas
- immune response
- dna binding
- chronic kidney disease
- papillary thyroid
- blood brain barrier
- high throughput
- binding protein
- pi k akt
- endoplasmic reticulum stress
- young adults
- patient reported outcomes
- childhood cancer
- case control