Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway.

ABSTRACT:

Backgound

Colorectal cancer (CRC) is a complex, multistep disease that arises from the interplay genetic mutations and epigenetic alterations. The histone H3K36 trimethyltransferase SET domain-containing 2 (SETD2), as an epigenetic signalling molecule, has a 5% mutation rate in CRC. SETD2 expression is decreased in the development of human CRC and mice treated with Azoxymethane /Dextran sodium sulfate (AOM/DSS). Loss of SETD2 promoted CRC development. SMAD Family member 4 (SMAD4) has a 14% mutation rate in CRC, and SMAD4 ablation leads to CRC. The co-mutation of SETD2 and SMAD4 predicted advanced CRC. However, little is known on the potential synergistic effect of SETD2 and SMAD4.

Methods

CRC tissues from mice and SW620 cells were used as research subjects. Clinical database

SUBMITTER: Ma C 

PROVIDER: S-EPMC10644329 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature