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.

SIRT6 suppresses colon cancer growth by inducing apoptosis and autophagy through transcriptionally down-regulating Survivin.

SIRT6, an evolutionarily conserved histone deacetylase, has been identified as a novel direct downstream target of Akt/FoxO3a and a tumor suppressor in colon cancer in our previous research. Nevertheless, the precise mechanisms through which SIRT6 hinders tumor development remain unclear. To ascertain whether SIRT6 directly impacts Survivin transcription, a ChIP assay was conducted using an anti-SIRT6 antibody to isolate DNA.

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.

Inhibition of AKT induces p53/SIRT6/PARP1-dependent parthanatos to suppress tumor growth.

Background: Targeting AKT suppresses tumor growth through inducing apoptosis, however, during which whether other forms of cell death occurring is poorly understood.

Methods: The effects of increasing PARP1 dependent cell death (parthanatos) induced by inhibiting AKT on cell proliferation were determined by CCK-8 assay, colony formation assay, Hoechst 33,258 staining and analysis of apoptotic cells by flow cytometry. For the detailed mechanisms during this process, Western blot analysis, qRT-PCR analysis, immunofluorescence and co-immunoprecipitation were performed.

Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway.

The most frequent genetic alterations of the TP53 gene in human cancer were reported. TP53 mutation gains new function as a target of genetic instability, which is associated with increased tumor progression and poor survival rate in patients. In this study, more than three hundred colorectal cancer patients' samples were firstly analyzed, and the results showed that patients with mutant p53 had higher levels of AKT phosphorylation and PD-L1 expression, which were next verified both in cell lines and patients' samples .

Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer.

In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal cancer growth by inducing cell death both in vitro and in vivo.

Chinese Therapists' Beliefs About Exposure Therapy for Anxiety and Obsessive-Compulsive Disorders.

Objectives: The goal of this study was to assess Chinese therapists' beliefs about exposure therapy and to examine the psychometric properties of the Chinese version of the Therapist Beliefs about Exposure Scale (TBES). Modification of therapists' beliefs about exposure therapy was also assessed following attendance at an exposure and response prevention therapy (ERP) training workshop.

Methods: A total of 203 therapists participated in the study.