Targeted regulation by ROCK2 on bladder carcinoma via Wnt signaling under hypoxia

Area of Science:

• Uro-oncology
• Molecular Biology
• Cellular Signaling

Background:

• Bladder cancer pathogenesis involves complex genetic and environmental factors, with hypoxia exacerbating tumor progression.
• ROCK2 (Rho-associated coiled-coil containing protein kinase 2) exhibits abnormal expression in various cancers, but its role in bladder cancer remains unclear.

Purpose of the Study:

• To investigate the expression and functional role of ROCK2 in bladder cancer cells under hypoxic conditions.
• To elucidate the impact of ROCK2 on bladder cancer cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT).

Main Methods:

• Utilized T24 bladder cancer cell line cultured under normoxic and hypoxic conditions.
• Employed ROCK2 siRNA for gene silencing in hypoxic cells.
• Assessed ROCK2, HIF-1α, E-cadherin, Wnt4, and β-catenin expression via Real-time PCR and Western blot.
• Quantified cell proliferation (MTT assay), migration (Transwell assay), and apoptosis (caspase-3 activity).

Main Results:

• ROCK2 expression was significantly upregulated in bladder cancer T24 cells under hypoxia.
• ROCK2 facilitated cell proliferation, migration, and invasion, while inhibiting apoptosis (decreased caspase-3 activity).
• ROCK2 enhanced HIF-1α expression, decreased E-cadherin, and upregulated Wnt4 and β-catenin, suggesting modulation of the Wnt signaling pathway and EMT.

Conclusions:

• ROCK2 plays a crucial role in promoting bladder cancer progression under hypoxic conditions.
• ROCK2 influences bladder cancer cell behavior by modulating the Wnt signaling pathway and EMT.
• Targeting ROCK2 may represent a potential therapeutic strategy for bladder cancer, particularly in hypoxic environments.