Jinghang Qian

The myocyte enhancer factor 2 (MEF2) transcription factor family plays crucial roles in differentiation, lineage specification, stress responses, and tissue homeostasis. Recent investigations have shown that the dysregulation of MEF2A, MEF2B, MEF2C, and MEF2D is associated with tumorigenesis, tumor progression, and adverse clinicopathological features in several cancers. MEF2B has a particularly important role in B-cell malignancies, where recurrent mutations deregulate BCL6 and promote lymphoma progression. MEF2A, MEF2C, and MEF2D also regulate malignant phenotypes, including proliferation, migration, invasion, apoptosis, drug resistance, angiogenesis, inflammation, and immune evasion, by the mechanism of regulating cell-cycle regulators, apoptosis-related genes, EMT-related genes, and other transcriptional programs. This review summarizes the mechanisms by which MEF2 family members contribute to tumor initiation and progression, with added emphasis on MEF2B mutations and MEF2D fusions. We also discuss clinical associations with overall survival and recurrence in solid tumors and hematologic malignancies. Because MEF2 proteins are transcription factors with broad physiological functions, we evaluate therapeutic strategies: RNA interference, genetic perturbation, small molecules that alter MEF2-dependent transcription, and PROTAC or oligonucleotide-PROTAC. These platforms remain promising but require MEF2-specific validation, tumor-selective delivery, and careful toxicity assessment.

Background: The intricate interplay between the platelet-coagulation system and the progression of malignant tumors has profound therapeutic implications. However, a thorough examination of platelet and coagulation markers specific to colorectal cancer (CRC) is conspicuously absent in the current literature. Consequently, there is an urgent need for further exploration into the mechanistic underpinnings of these markers and their potential clinical applications. Methods: By integrating RNA-seq data and clinicopathological information from patients with CRC in the cancer genome atlas, we identified genes related to the platelet-coagulation system using weighted gene co-expression networks and univariate Cox analysis. We established a prognostic risk model based on platelet- and coagulation-related genes using Lasso Cox regression analysis and validated the model in two independent CRC cohorts. We explored potential biological functional disparities between high-risk and low-risk groups through comprehensive bioinformatics analysis. Results: Our findings indicate that colorectal cancer patients classified as high-risk generally exhibit poorer prognoses. Moreover, the model’s risk scores were associated with the differential composition of the immune tumor microenvironment, suggesting its applicability to infer immunotherapy responsiveness. Cellular functional experiments and animal experiments indicated that CYP19A1 expression in CRC influences malignant phenotype and platelet activation. Conclusions: In summary, we present a novel platelet- and coagulation-related risk model for prognostic assessment of patients with CRC and confirm the important role of CYP19A1 in promoting malignant progression of CRC.