HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

Area of Science:

• Oncology
• Molecular Biology
• Gene Regulation

Background:

• Histone deacetylase 3 (HDAC3) is implicated in colorectal cancer (CRC) pathogenesis.
• The specific feedback loop involving HDAC3, microRNA (miR)-296-3p, and transforming growth factor β-induced factor 1 (TGIF1) in CRC remains unclear.

Purpose of the Study:

• To elucidate the mechanism of the HDAC3/miR-296-3p/TGIF1 axis in colorectal cancer progression.
• To investigate the regulatory role of HDAC3 on the miR-296-3p/TGIF1/TGFβ pathway in CRC.

Main Methods:

• Utilized a comprehensive approach including in vitro, in vivo, and clinical sample analyses.
• Employed techniques such as RT-qPCR, Western blot, cell proliferation/invasion assays, and nude mouse xenografts.
• Investigated gene interactions using dual luciferase reporter and chromatin immunoprecipitation assays.

Main Results:

• CRC tissues exhibited higher HDAC3 and TGIF1, and lower miR-296-3p expression.
• HDAC3 positively correlated with TGIF1 and negatively with miR-296-3p; miR-296-3p negatively correlated with TGIF1.
• HDAC3 depletion or miR-296-3p restoration inhibited CRC proliferation, invasion, migration, and tumor growth, while TGIF1 overexpression reversed these effects.

Conclusions:

• Down-regulation of HDAC3 or TGIF1, or up-regulation of miR-296-3p, inhibits CRC cell progression and tumor growth.
• This axis presents a potential novel therapeutic target for colorectal cancer treatment.