CDKN1B (Cyclin dependent kinase inhibitor 1B)

In this exploratory analysis, we found that Black men have improved survival in the first line mCRPC setting with ARPI therapy, but that SPOP mutations do not explain these differential outcomes despite improved short term PSA declines. Thus, other factors may explain the disparity in outcomes we confirmed in men with CRPC.

This led to the downregulation of key oncogenic effectors including Slug, FN1, CDH2, F2RL1, CDK6, CCND1, MMP9, CDKN2A, and SQSTM1, while upregulating tumor suppressors CDKN1B, CDKN1A, and DDIT3. In conclusion, COPB2 acts as an oncogene in GC, driving tumor progression through modulation of the cell cycle and key signaling pathways, highlighting its potential as a therapeutic target.

Molecular docking simulations suggested potential direct interactions between monoethyl phthalate and their protein products. Our findings propose 10 genes as potential mediators of monoethyl phthalate-induced thyroid cancer, with ESR1, SKP2, CASP8, ARNT, and CDKN1B highlighted as core factors potentially involved in thyroid cancer pathogenesis.

Paeoniflorin induces melanoma cell senescence through the ER stress/calpain1/ERK5/p27 signaling axis, suggesting its potential as a novel therapeutic strategy against SKCM.

We show that the KRAS-G12C inhibitor Sotorasib synergizes with the CDK4/6 inhibitor Palbociclib to eliminate pancreatic ductal adenocarcinoma (PDAC) cells and organoids harboring KRAS-G12C mutations...Additionally, the KRAS-G12D inhibitor MRTX1133 cooperated with Palbociclib to suppress growth of KRAS-G12D-mutant PDAC cells...Single-cell RNA sequencing suggested that Palbociclib treatment induces tumor vascularization, perhaps contributing to the lack of drug synergy observed in vivo. In summary, our findings demonstrate the therapeutic potential of enhancing cell cycle restriction point activation in KRAS inhibitor-based therapies, while emphasizing the importance of placing combination therapies into a suitable context.

MiR-145 directly bound to DLX6, reducing its mRNA and protein levels and effectively counteracting DLX6's oncogenic effects. Collectively, these findings uncovered a previously uncharacterized role of DLX6 in LUAD development and proposed the miR-145/DLX6/p27Kip1/CDK2-CyclinE signal axis as a potential therapeutic target for LUAD management.

In conclusion, our findings emphasize the critical role of p27 in triggering ferroptosis, thereby sensitizing EOC cells to cisplatin therapy. These results suggest that therapeutic strategies aimed at enhancing p27 levels may represent a promising approach to overcoming chemoresistance in EOC.

Furthermore, Western blot analysis revealed that both compounds significantly inhibited the phosphorylation of the EGFR (pEGFR) and also upregulated the expression of LC3B-II (a key marker of autophagy) and cyclin-dependent kinase inhibitor p27, suggesting that activation of autophagy and cell cycle arrest occurred, respectively, thereby inhibiting EGFR phosphorylation and activating downstream cellular responses similar to those of Erlotinib...In silico ADME profiling further highlighted favourable pharmacokinetic properties, reinforcing the potential of 4d and 6d as promising lead candidates. Collectively, these results establish fused thiophene-benzimidazole hybrids as selective EGFR-targeted anticancer agents with strong therapeutic promise.

Skp2-overexpressing A549 cell xenografts were also more sensitive to CPT than A549 cell xenografts with empty vector; tumors with high Skp2 levels exhibited lower p27 expression and greater DNA damage after CPT treatment. Collectively, our study demonstrated that the CPT induces p27 accumulation by targeting Skp2, whereas Skp2 overexpression can modulate the off-target effects and enhance CPT sensitivity in NSCLC, supporting the potential use of Skp2 as a predictive biomarker for CPT-based therapy.

PIK3R2 ectopic expression overcame the cellular effects of CyKILRb downregulation, but not PI 3 K or AKT inhibition orienting the signaling pathway from CyKILRb→↑PIK3R2→PI3K→AKT→↓CyKILRa→enhanced oncogenicity. These findings highlight the critical role of CyKILRb in tumorigenesis and define a novel feed-forward regulatory mechanism linked to alternative RNA splicing.

This atlas provides the most comprehensive transcriptional profiling of the developing inner ear, identifying new molecular leads to understand ear morphogenesis. Single-cell transcriptomic analysis of developing wild-type and lmx1bb mutant zebrafish reveals cell-states and effectors that distinguish the inner ear's sensory patches, semicircular canals, endolymphatic duct and sac, and periotic mesenchyme.

In conclusion, MEN1 phenocopies are relatively common and represent a clinical challenge. Given their distinct features and familial backgrounds, an extended genetic panel should be offered to these patients together with periodical screening of MEN1-related disease.