Background/Aims: The Wnt signaling pathway has essential functions in the central nervous system, where it regulates the major physiological functions of neurons, including development, differentiation, and plasticity. Wnt signaling controls these cellular events; however, how Wnt pathways integrate into a coherent developmental program remains unclear. Methods: The expression and secretion of different WNT ligands (Wnt-1, Wnt-3a, Wnt-4, Wnt-5a, Wnt-11), and the levels and activities of cyclin-dependent kinases (CDK2, CDK4, CDK6/cyclin D, cyclin E) or CDK5 (CDK5/p35 and p25) were measured in Rat cortex at different embryonic stages, and in RA/BDNF-induced differentiated SH-SY5Y cell model, by Quantitative real-time PCR (qPCR), western blotting, ELISA, and in vitro CDK5 kinase assays. MAP2-BrdU double staining was used to assess cell differentiation and cell cycle exit in an RA/BDNF-induced differentiated SH-SY5Y cell model. The effects of CDK5 and Ca²⁺/calpain signaling were assessed using specific chemical inhibitors. Results: We found that Wnt-1 was unchanged and Wnt-3a was attenuated, whereas Wnt-4, Wnt-5a, and Wnt-11 were markedly up-regulated, during the development of neurons and differentiated SH-SY5Y cells. Simultaneously, the activity of CDK5 was elevated. Furthermore, we describe crosstalk between non-canonical Wnt signaling and CDK5 in the development of neurons and differentiated SH-SY5Y cells. Wnt-5a, a non-canonical Wnt ligand, regulated CDK5 via Ca²⁺/calpain signaling in both neuronal development and differentiation. Inhibition of Wnt-5a diminished CDK5 kinase activity via the Ca²⁺/calpain pathway, thereby attenuating RA-BDNF induced SH-SY5Y cell differentiation. Conclusion: Wnt-5a signaling is a significant regulator of neuronal development and differentiation and upregulates CDK5 kinase activity via Ca²⁺/calpain signaling.

Breast cancer (BC) is widely recognized as the most frequently diagnosed neoplasm among women worldwide. Despite significant advances, improved diagnosis and treatment of breast cancer have failed to translate into earlier detection or markedly better outcomes for patients, due to challenges including late-stage presentation, metastasis, recurrence, metabolic reprogramming, and drug resistance. Identifying reliable predictive indicators for early intervention and diagnostic markers remains a priority in breast cancer research, as this is crucial for improving patient prognosis. Circular RNAs (circRNAs), a class of non-coding RNAs (ncRNAs) abundant in various tissues and human cells, are established biomarkers for diagnosing and monitoring diseases such as those affecting the nervous, cardiovascular, and immune systems. CircRNAs contribute to tumorigenesis through the regulation of proliferation, metastasis, angiogenesis, and the tumor microenvironment. A growing body of evidence has established circRNAs as key regulators in breast cancer, elucidating their specific roles in driving tumor development and progression. Nevertheless, a more comprehensive understanding of the functional roles and molecular mechanisms of circRNAs in BC is essential and requires further research. This narrative review synthesizes the current knowledge on circRNAs encompassing their biogenesis, characteristics, methylation, tumor cell death, and selectively analyzes the translational potential of circRNAs in BC patients.

Background: Hypoxia contributes to the proliferation, migration, and chemotherapy resistance of lung adenocarcinoma (LUAD). This study aimed to identify hypoxia-related genes (HRGs) in LUAD that were positively correlated with hypoxia-inducible factor 1 alpha (HIF1A), to advance the diagnosis and treatment of this specific type of cancer. Methods: The transcriptome data were retrieved from the Gene Expression Omnibus (GEO). Multiple bioinformatics analysis methods were employed to identify HRGs that were upregulated in LUAD samples and positively correlated with the expression of HIF1A. Machine Learning algorithms were utilized for optimized selection, filtering out core HRGs highly associated with the disease. Finally, in vitro experiments confirmed the expression of these core HRGs in LUAD cells under hypoxic conditions. Results: The study revealed five core HRGs that exhibit a positive correlation with HIF1A [collagen type I alpha 1 chain (COL1A1), interleukin 11 (IL11), matrix metallopeptidase 14 (MMP14), notch receptor 3 (NOTCH3), and thymocyte differentiation antigen 1 (THY1)]. In vitro experiments conducted on A549 cells demonstrated a marked increase in mRNA expression for both the identified core HRGs and HIF1A following chronic intermittent hypoxia (CIH) treatment. The developed model exhibits substantial predictive efficacy for assessing the prognosis of LUAD patients experiencing concurrent hypoxia. Conclusions: The five HRGs that we have identified as positively associated with HIF1A may serve as crucial targets for promoting the progression of LUAD under hypoxic conditions. This discovery offers valuable insights into the diagnosis and treatment of clinical hypoxic disease in patients with LUAD.