BAP31 Promotes Epithelial-Mesenchymal Transition Progression Through the Exosomal miR-423-3p/Bim Axis in Colorectal...

Area of Science:

• Molecular Biology
• Cancer Research
• Cell Biology

Background:

• Colorectal cancer (CRC) progression is linked to epithelial-mesenchymal transition (EMT).
• Exosomes play a crucial role in intercellular communication and cancer progression.
• The regulatory mechanisms of exosomal miRNA in CRC-associated EMT remain incompletely understood.

Purpose of the Study:

• To investigate the role of BAP31 in regulating exosomal miRNA content.
• To determine the impact of BAP31-mediated exosomal miRNA changes on EMT in CRC.
• To elucidate the molecular mechanisms underlying BAP31's function in CRC progression.

Main Methods:

• Overexpression (OE) and knockdown (sh) of BAP31 in CRC cells.
• Exosome isolation and characterization.
• Cell migration assays and EMT marker analysis (E-cadherin, N-cadherin, Vimentin).
• miRNA profiling and bioinformatics analysis.
• Luciferase reporter assays and Western blot analysis.
• In vivo tumor growth inhibition studies.

Main Results:

• Exosomes from BAP31-OE cells promoted migration and EMT, while exosomes from shBAP31 cells inhibited these processes.
• miR-423-3p was identified as a key exosomal miRNA regulated by BAP31, mediating EMT.
• BAP31 facilitates exosomal sorting of miR-423-3p via the RNA export adaptor Alyref.
• The miR-423-3p/Bim signaling axis was confirmed as a critical pathway in BAP31-induced EMT.
• shBAP31 exosomes significantly inhibited tumor growth in vivo.

Conclusions:

• BAP31 selectively sorts exosomal miR-423-3p through Alyref, promoting EMT in CRC.
• The miR-423-3p/Bim axis is a key mediator of BAP31's pro-tumorigenic effects.
• BAP31 represents a potential therapeutic target for inhibiting EMT and tumor progression in CRC.