miR-344-5p Modulates Cholesterol-Induced β-Cell Apoptosis and Dysfunction Through Regulating Caveolin-1 Expression

Area of Science:

• Endocrinology
• Molecular Biology
• Metabolic Disorders

Background:

• Type 2 diabetes mellitus (T2DM) involves islet beta-cell dysfunction.
• MicroRNAs (miRNAs) are implicated in T2DM pathogenesis.
• miR-344's role in diabetes requires further elucidation.

Purpose of the Study:

• Investigate the role of miR-344 in cholesterol-induced pancreatic beta-cell dysfunction.
• Determine the molecular mechanisms underlying miR-344's effects.
• Explore miR-344 as a potential therapeutic target for T2DM.

Main Methods:

• Bioinformatics analysis and literature review.
• In vitro studies using cholesterol- and palmitic acid-stimulated rat islet beta-cells.
• Overexpression and inhibition of miR-344-5p.
• Analysis of cell viability, glucose-stimulated insulin secretion (GSIS), apoptosis markers (caspase 3/Bax), and signaling pathways (MAPK/ERK).
• Cav1 gene silencing and its effects.

Main Results:

• miR-344-5p expression is decreased in cholesterol- and PA-induced beta-cell dysfunction.
• miR-344-5p overexpression attenuated cholesterol/PA-induced beta-cell damage, improved GSIS, and reduced lipid deposition.
• miR-344-5p inhibited apoptosis via caspase 3/Bax signaling and protected against cholesterol-induced dysfunction via MAPK/ERK signaling.
• miR-344-5p directly targets Cav1, and Cav1 silencing partially reversed miR-344 inhibition effects.

Conclusions:

• The miR-344-5p/Cav1 axis plays a critical role in modulating cholesterol-induced beta-cell apoptosis and dysfunction.
• miR-344-5p exhibits protective effects against T2DM-related beta-cell damage.
• The caspase 3/Bax and MAPK/ERK signaling pathways are involved in miR-344-5p-mediated protection.