Immunogenic cuproptosis in cancer immunotherapy via an in situ cuproptosis-inducing system.

Cell death-based therapies combined with immunotherapy have great potential in cancer therapy. To further explore and apply the combined therapies, the immunogenicity of different cell death modes in colorectal cancer (CRC) was evaluated by a cause-and-effect framework encompassing 12 cell death modes. Results show robust correlations among cuproptosis, immunogenic cell death (ICD) and immunity in CRC, as observed in our in-house and other independent cohorts, which are substantiated by in vitro and in vivo experiments.

LncRNA CARMN m6A demethylation by ALKBH5 inhibits mutant p53-driven tumour progression through miR-5683/FGF2.

N-methyladenosine (m6A) represents a prevalent RNA modification observed in colorectal cancer. Despite its abundance, the biological implications of m6A methylation on the lncRNA CARMN remain elusive in colorectal cancer, especially for mutant p53 gain-of-function. Here, we elucidate that CARMN exhibits diminished expression levels in colorectal cancer patients with mutant p53, attributed to its rich m6A methylation, which promotes cancer proliferation, invasion and metastasis in vitro and in vivo.

Targeting AKT induced Ferroptosis through FTO/YTHDF2-dependent GPX4 m6A methylation up-regulating and degradating in colorectal cancer.

Ferroptosis is a new type of iron-dependent programmed cell death induced by lipid peroxidation. However, the underlying mechanisms and function in tumor therapy still remain undisclosed especially in post-transcription regulation. Here, we found that targeting AKT significantly induced GPX4 dependent ferroptosis and suppressed colorectal cancer growth both in vitro and in vivo.