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Colorectal cancer (CRC) is the third most common cancer worldwide and has an increasing incidence in younger populations. The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, the role and contribution of the distinct family members in regulating CRC tumorigenesis has not been addressed yet. Herein, we used publicly available CRC patient datasets (TCGA RNA sequence) and several bioinformatics webtools to perform in silico analysis (GTEx, GENT2, GEPIA2, cBioPortal, GSCALite, TIMER2, and UALCAN). We aimed to investigate the DYRK family member expression pattern, prognostic value, and oncological roles in CRC. This study shed light on the role of distinct DYRK family members in CRC and their potential outcome predictive value. Based on mRNA level, DYRK1A is upregulated in late tumor stages, with lymph node and distant metastasis. All DYRKs were found to be implicated in cancer-associated pathways, indicating their key role in CRC pathogenesis. No significant DYRK mutations were identified, suggesting that DYRK expression variation in normal vs. tumor samples is likely linked to epigenetic regulation. The expression of DYRK1A and DYRK3 expression correlated with immune-infiltrating cells in the tumor microenvironment and was upregulated in MSI subtypes, pointing to their potential role as biomarkers for immunotherapy. This comprehensive bioinformatics analysis will set directions for future biological studies to further exploit the molecular basis of these findings and explore the potential of DYRK1A modulation as a novel targeted therapy for CRC.

Targeting cell cycle and inducing DNA damage by activating cell death pathways are considered as effective therapeutic strategy for combating breast cancer progression. Many of the naturally known small molecules target these signaling pathways and are effective against resistant and/or aggressive types of breast cancers. Here, we investigated the effect of catechol, a naturally occurring plant compound, for its specificity and chemotherapeutic efficacies in breast cancer (MCF‐7 and MDA‐MB‐231) cells. Catechol treatment showed concentration‐dependent cytotoxicity and antiproliferative growth in both MCF‐7 and MDA‐MB‐231 cells while sparing minimal effects on noncancerous (F‐180 and HK2) cells. Catechol modulated differential DNA damage effects by activating ATM/ATR pathways and showed enhanced γ–H2AX expression, as an indicator for DNA double‐stranded breaks. MCF‐7 cells showed G1 cell cycle arrest by regulating p21‐mediated cyclin E/Cdk2 inhibition. Furthermore, activation of p53 triggered a caspase‐mediated cell death mechanism by inhibiting regulatory proteins such as DNMT1, p‐BRCA1, MCL‐1, and PDCD6 with an increased Bax/Bcl‐2 ratio. Overall, our results showed that catechol possesses favorable safety profile for noncancerous cells while specifically targeting multiple signaling cascades to inhibit proliferation in breast cancer cells.

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