BACKGROUND:Association of the BCL11A (rs4671393), HBG2 (rs7482144), and HBG2HBS1L-MYB (rs28384513, rs9399137, and rs4895441) variants with susceptibility to thalassemia was observed. METHODOLOGY:Blood samples from 600 individuals, including 300 thalassemia patients and 300 controls, age- and gender-matched, were collected. DNA was extracted, followed by DNA Amplification. RESULTS:Results show that the homozygous mutant (GG) of variant rs4671393 of the BCL11A gene showed a strong association with increased risk of thalassemia by 3-fold (OR = 3.05; p = 0.0002), heterozygous (AG) also showed a strong association but with a decreased risk (OR = 0.49; p = 0.0028). The heterozygote (AC) and the mutant of variant rs28384513 of gene HBG2HBS1L-MYB showed a significant association by increasing the risk of thalassemia by 2-fold (OR = 2.07; p = 0.001; OR = 2.79; p = 0.0002, respectively). In the case of rs4895441 of gene HBS1L-MYB, the AG heterozygote showed a significant association by increasing the risk by 2.55-fold (OR = 2.55; p = 0.0002). For gene HBG2, the heterozygote (CT) of the rs7482144 variant significantly decreased the risk of thalassemia (OR = 0.37; p = 0.0001). Its homozygous mutant (TT) also showed a significant association, but with an increased risk of thalassemia by 2-fold (OR = 1.81; p = 0.036). . CONCLUSION:The polymorphisms rs4671393 (BCL11A), rs7482144 (HBG2), and rs28384513, rs9399137, and rs4895441 (HBS1L-MYB) are significantly associated with an increased risk of thalassemia.
OBJECTIVE:This work aims to analyze the clinical significance of microRNA-27a-3p (miR-27a-3p) in hepatocellular carcinoma (HCC) and its impact on HCC cell behavior. METHODS:RT-qPCR was performed on 57 paired HCC tumor and adjacent normal tissues to assess miR-27a-3p levels and its correlation with prognosis and clinicopathological features. HCC cells were transfected with miR-27a-3p inhibitor/mimic, si-TET1, or corresponding controls. RT-qPCR/Western blot measured miR-27a-3p, TET1, and p53 levels. CCK-8/Transwell/flow cytometry assay evaluated cell activities. Dual-luciferase reporter and RNA pull-down assays confirmed the direct interaction between miR-27a-3p and TET1. In vivo, a subcutaneous xenograft model was used to assess the effect of miR-27a-3p antagomir on tumor growth via tail vein injection. RESULTS:miR-27a-3p was upregulated in HCC tissues, correlating with poor survival, TNM stage, tumor size, alongside vascular invasion. miR-27a-3p knockdown diminished HCC cell growth while promoting apoptosis. Mechanistically, miR-27a-3p targeted TET1. Rescue experiments reflected that TET1 inhibition partially reversed the tumor-suppressive impacts of miR-27a-3p silencing. Further, miR-27a-3p knockdown enhanced p53 levels via TET1, whereas its overexpression suppressed both TET1 and p53. In vivo, miR-27a-3p antagomir suppressed HCC xenograft tumor growth. CONCLUSION:Downregulation of miR-27a-3p exerts a tumor-suppressive impact in HCC by inhibiting malignant biological behaviors, potentially via the TET1/p53 axis.
AIM:Colorectal cancer (CRC) is a widespread health issue that attains high mortality. The adaptor protein SH3BP2 amplification results in metabolic changes, oxidative stress, NK cell activity, and inflammation. The NK cells are capable of destroying tumor cells without prior activation, help prevent metastasis, and have prognostic value. Targeting SH3BP2 to regulate NK cell activity in the TME could enhance CRC-based immunotherapy. MATERIALS AND METHODS:The cancer hallmark tool helps in understanding SH3BP2 hallmark annotation. Utilizing the STRING tool and the KEGG pathway, protein functional enrichment and PPI networking were analyzed. TIMER 2.0 was used for immune cell infiltration correlation analysis, and UALCAN was used for CPTAC-based protein expression profiling. RESULTS AND CONCLUSIONS:The GEO (GSE9348) dataset showed SH3BP2 is upregulated in CRC (log2 fold change = 1.18). GEO, TCGA, and cBioPortal revealed SH3BP2 alterations in CRC cases, potentially aiding immune evasion. Mutations in SH3BP2 influence cancer growth, suppressing tumors or promoting them by activating NF-κB and affecting immune responses through WNT/β-catenin, PI3K, MAPK, and JAK-STAT pathways. Overall, SH3BP2 plays a key role in cancer growth and immune regulation, making it a promising target for CRC therapy. Further experimental validation is needed to demonstrate its diagnostic and therapeutic potency.
BACKGROUND:Dapsone is a drug used to treat leprosy. Dapsone causes a highly morbid and potentially fatal severe drug hypersensitivity reaction (DHS) in 1-3% of leprosy cases. The allele HLA-B*13:01 is a known genetic risk factor for DHS. However, resource-intensive genotyping methods preclude its testing in resource-limited settings. This study aimed to develop an endpoint PCR assay to detect the presence of HLA-B*13:01. RESEARCH DESIGN AND METHODS:DNA was extracted from blood samples of leprosy patients at Anandaban Hospital, Nepal (2022-24). A duplex endpoint PCR was optimized and validated against a previously validated commercial qPCR method and NGS (next‑generation sequencing). RESULTS:In 113 samples, duplex PCR showed 100% (95% CI: 79.4-100%) sensitivity and 100% specificity (95% CI: 96.2-100%) compared to the validated qPCR method. The same accuracy was confirmed in 58 NGS-typed samples (concordance 98.3%, 95% CI: 90.7-99.9%). The assay reliably differentiated HLA-B*13:01 from closely related allele. Analytical sensitivity reached a lower detection limit of 100 genome equivalents (0.67 ng DNA/reaction). CONCLUSION:The developed duplex endpoint PCR offers a simple and affordable method for detecting HLA-B*13:01, suitable in low-resource settings. Its use may significantly reduce the risk of DHS by guiding safer drug choices prior to MDT initiation.
