KNSTRN knockdown impairs autophagy flux to inhibit bladder cancer progression

Area of Science:

• Oncology
• Cell Biology
• Molecular Mechanisms

Background:

• Bladder cancer (BLCA) is a prevalent urinary system malignancy.
• Kinetochore-localized astrin-binding protein (KNSTRN) is linked to various cancer developments.
• Dysregulated autophagy significantly influences tumor progression.

Purpose of the Study:

• To elucidate the mechanism by which KNSTRN regulates autophagy in BLCA.
• To investigate the role of KNSTRN in BLCA progression and autophagy flux.

Main Methods:

• Investigated KNSTRN knockdown effects on autophagy flux in BLCA cells.
• Assessed the role of reactive oxygen species (ROS) and lysosomal function.
• Utilized Clioquinol to restore lysosomal activity and N-acetylcysteine (NAC) as a ROS scavenger.
• Employed rapamycin (Rapa) as an autophagy activator in vitro and in vivo.

Main Results:

• KNSTRN knockdown significantly inhibited autophagy flux in BLCA.
• ROS accumulation and lysosomal dysfunction were observed upon KNSTRN knockdown, impeding autophagosome-lysosome fusion.
• Clioquinol and NAC treatments reversed lysosomal dysfunction and restored autophagy flux.
• Rapamycin counteracted KNSTRN knockdown-induced cell death in vitro and in vivo.

Conclusions:

• KNSTRN knockdown disrupts BLCA progression by inducing ROS and lysosomal dysfunction, thereby inhibiting autophagic flux.
• Targeting ROS and restoring lysosomal function presents a potential therapeutic strategy for BLCA.