Ahmad Sami

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by uncontrolled proliferation of myeloid cells. MicroRNAs (miRNAs), small noncoding RNAs, regulate post-transcriptional gene expression by degrading target mRNAs or repressing translation. Dysregulated miRNA expression has been implicated in various malignancies, including CML, where they can function as oncogenes or tumor suppressors. This study aimed to investigate the relationship between miR-122-5p and cell division cycle 25A (CDC25A) in CML and to elucidate the regulatory mechanisms of miR-122-5p. This study integrates bioinformatics analysis with in vitro RT-qPCR validation in K562 chronic myeloid leukemia cells to explore the potential regulatory relationship between miR-122-5p and CDC25A. mRNA expression profiles were retrieved from the GSE100026 dataset in the Gene Expression Omnibus (GEO), and differentially expressed genes were identified using GEO2R. Quantitative real-time PCR (RT-qPCR) was performed to measure miR-122-5p, CDC25A, and cyclin-dependent kinase 4 (CDK4) expression levels. Bioinformatics analyses (miRNeT, miRDIP, TargetScan, BioGPS, GeneMANIA, STRING) were applied to predict molecular interactions and functional pathways. Public RNA-seq datasets and in silico tools were used to prioritize candidates; RT-qPCR in a single CML cell line (K562) provided in vitro expression validation. In K562 cells, miR-122-5p expression was significantly reduced, while CDC25A and CDK4 were markedly upregulated. Bioinformatics tools confirmed CDC25A as a potential miR-122-5p target. Functional enrichment indicated CDC25A involvement in cell cycle regulation and apoptosis. These findings suggest that miR-122-5p functions as a tumor suppressor in CML by targeting CDC25A. Modulating the miR-122-5p/CDC25A axis may provide potential molecular targets for inhibiting CML progression through regulation of cell cycle pathways. Findings are exploratory and based on bioinformatics with limited in vitro expression confirmation; functional studies are required to establish causality.

PD-L1, PD-1, FOXP3, and miR-155 are emerging as key modulators of immune evasion and progression of oral squamous cell carcinoma (OSCC). This study investigated the clinical relevance of their gene expression and variants in HPV-negative OSCC. Bulk-tissue mRNA expression was evaluated in 70 patients, while variants in PD-1 (rs36084323), PD-L1 (rs822336, rs4143815, copy number variation), FOXP3 (rs3761548, rs2232365), and miR-155 (rs767649) were assessed in 134 patients. Expression data were validated using the TCGA cohort of 222 HPV-negative OSCC cases. Low FOXP3 expression was significantly associated with tumor stage (MMA: p = 0.028, TCGA: p = 0.025) and poor overall survival (MMA: p = 0.0004, TCGA: p = 0.019) in both cohorts. Declining FOXP3 expression correlated with advancing tumor stages, and low FOXP3 expression was significantly associated with poor survival in advanced stage III–IV tumors (MMA: p = 0.001, TCGA: p = 0.015), but not early-stage tumors. High miR-155 expression was associated with recurrence (p = 0.002) and poor survival in the MMA (p = 0.007), but not TCGA cohort. MiR-155 rs767649 was associated with alcohol consumption (p = 0.018). These findings point to FOXP3 and miR-155 as potential prognostic biomarkers for HPV-negative OSCC. Stage-specific FOXP3 expression suggests a dynamic immunoregulatory role, with implications for optimizing immunotherapy timing. Further studies are warranted to resolve cellular context and stage-adapted immune interventions in HPV-negative OSCC.

Acute myeloid leukemia (LAML) is one of the most prevalent hematological malignancies. In recent years, while targeted approaches have shown promise in the fight against cancer, the treatability and prognosis of patients remain inadequate due to the shortage of drugs. Noncoding RNAs, especially circular RNA (circRNA) and microRNA (miRNA), have been shown to play a unique role in tumor development. This study aims to identify the disease-associated circRNA–miRNA–mRNA network by bioinformatic analysis and investigate the mechanisms in the development and progression of LAML. Additionally, it reveals the promising roles of these molecules as a diagnostic biomarker and therapeutic target for LAML treatment. Using various bioinformatics approaches, we identified the hsa_circ_0058058/miR-324-5p axis in LAML and its possible functions in LAML development. According to our results, hsa circ-0058058 can regulate the expression of AP1G1 and SP1 through miR-324-5p to support angiogenesis, the cell cycle, and DNA replication processes. Downregulation of hsa circ-0058058 may contribute to the anticancer functions of miR-324-5p on LAML tumorigenesis, and upregulation of miR-324-5p can abolish the oncogenic effects of AP1G1 and SP1 on LAML tumorigenesis. Additionally, highly enriched pathways indicated possible interactions between molecules underlying LAML pathology. Targeted molecules within this network may be able to function as therapeutic and diagnostic biomarkers for disease, while more research and clinical confirmation are needed.