RESUMO
Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.
Assuntos
Proliferação de Células , Neoplasias Colorretais , Peptidase 7 Específica de Ubiquitina , Fator de Transcrição YY1 , Humanos , Fator de Transcrição YY1/metabolismo , Fator de Transcrição YY1/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Peptidase 7 Específica de Ubiquitina/metabolismo , Peptidase 7 Específica de Ubiquitina/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Animais , Metástase Neoplásica , Camundongos Nus , Ubiquitinação , Camundongos , Movimento Celular , Masculino , Ligação ProteicaRESUMO
The Charcot-Marie-Tooth disease (CMT) is one of the most common human inherited peripheral neuropathies. The most common pattern of inheritance is autosomal dominant, with less often occurrence autosomal recessive and X-linked dominant/recessive inheritance. CMT is generally divided into three forms: demyelinating forms (CMT1), axonal forms (CMT2) and intermediate forms (DI-CMT). The autosomal recessive form (AR-CMT1 or CMT4) is accompanied by progressive distal muscle weakness and atrophy of the limbs, pes cavus and claw-like hands. In addition, CMT4 is also characterized by early onset, rapid progression, and varying degrees of sensory loss and spinal deformities (e.g. scoliosis). Recently, 11 subtypes of CMT4 have been identified. Some of these subtypes were clear in pathogenic mechanisms, some had founder mutation, but some still had limited clinical description and mutation analysis. In this review, we summarize the latest research progresses of CMT4, including genotypes and phenotypes, pathogenic mechanisms and mouse models.
