RESUMO
Pre-B-cell leukaemia transcription factor (PBX) proteins are a subfamily of evolutionarily conserved, atypical homeodomain transcription factors that belong to the superfamily of three amino acid loop extension (TALE) homeodomain proteins. Members of the PBX family play crucial roles in regulating multiple pathophysiological processes, such as the development of organs, congenital cardiac defects and carcinogenesis. The dysregulation of PBXs has been shown to be closely associated with many diseases, particularly cancer. However, the detailed mechanisms of PBX dysregulation in cancer progression are still inconclusive. In this review, we summarize the recent advances in the structures, functions and regulatory mechanisms of PBXs, and discuss their underlying mechanisms in cancer progression. We also highlight the great potential of PBXs as biomarkers for the early diagnosis and prognostic evaluation of cancer as well as their therapeutic applications. The information reviewed here may expand researchers' understanding of PBXs and could strengthen the clinical implication of PBXs in cancer treatment.
Assuntos
Proteínas de Homeodomínio , Neoplasias , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Neoplasias/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B , Fatores de Transcrição/metabolismoRESUMO
Cancer is the second-leading disease-related cause of global mortality after cardiovascular disease. Despite significant advances in cancer therapeutic strategies, cancer remains one of the major obstacles to human life extension. Cancer pathogenesis is extremely complicated and not fully understood. Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, belong to the heterogeneous nuclear ribonucleoprotein family of RNA-binding proteins and are crucial regulators of the alternative splicing of messenger RNAs (mRNAs). The expression and activity of ESRPs are modulated by various mechanisms, including post-translational modifications and non-coding RNAs. Although a growing body of evidence suggests that ESRP dysregulation is closely associated with cancer progression, the detailed mechanisms remain inconclusive. In this review, we summarize recent findings on the structures, functions, and regulatory mechanisms of ESRPs and focus on their underlying mechanisms in cancer progression. We also highlight the clinical implications of ESRPs as prognostic biomarkers and therapeutic targets in cancer treatment. The information reviewed herein could be extremely beneficial to the development of individualized therapeutic strategies for cancer patients.
Assuntos
Neoplasias , Splicing de RNA , Humanos , Processamento Alternativo , Neoplasias/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , RNA Mensageiro/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Biomarcadores/metabolismoRESUMO
Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients' health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are widely involved in the regulation of cancer drug resistance. Their dysregulation contributes to the development of cancer drug resistance by modulating the expression of specific target genes involved in cellular apoptosis, autophagy, drug efflux, epithelial-to-mesenchymal transition (EMT), and cancer stem cells (CSCs). Moreover, some ncRNAs also possess great potential as efficient, specific biomarkers in diagnosis and prognosis as well as therapeutic targets in cancer patients. In this review, we summarize the recent findings on the emerging role and underlying mechanisms of ncRNAs involved in cancer drug resistance and focus on their clinical applications as biomarkers and therapeutic targets in cancer treatment. This information will be of great benefit to early diagnosis and prognostic assessments of cancer as well as the development of ncRNA-based therapeutic strategies for cancer patients.