23 DOI: https://doi.org/10.1016/j.jgeb.2026.100678 English eng Farouk, Sally Contributor <div class="u-margin-s-bottom" id="sp0010" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px; margin-bottom: 16px !important;">Hepatocellular carcinoma (HCC) is ranked globally as the second most common cancer-related death. Transforming growth factor beta (TGF-β) plays a dual role in HCC. Meanwhile, miR-let-7c has been identified as a tumor suppressor microRNA that regulates oncogenic pathways, including the TGF-β signaling cascade. Dysregulation of miR-let-7c may enhance TGF-β1 overproduction, sustaining oncogenic signaling and accelerating HCC progression. To investigate the impact of TGF-β gene variants and the relative expression of miR-let-7c on TGF-β production in HCC patients. A total of 150 HCC patients and 50 healthy controls were enrolled. DNA was extracted for TGF-β genotyping, serum TGF-β1 levels were quantified using an ELISA assay, and miR-let-7c expression was assessed by quantitative real-time PCR (qRT-PCR). In silico analysis was performed to confirm interactions.</div><div class="u-margin-s-bottom" id="sp0015" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px; margin-bottom: 16px !important;">Our results revealed that HCC patients had TT genotype (59%), while the control group TT genotype represents (16%,) with high significance differences between control and HCC patients (P = 0.0001). TGF-β was significantly elevated in the HCC group (366 ± 111.8 pg/mL) versus controls (100 ± 26.57 pg/mL, P < 0.0001). The relative expression of circulating miR-let-7c was significantly downregulated in HCC patients compared to the control group (P = 0.0001). TGF-β demonstrated high diagnostic accuracy (AUC = 0.9907, P = 0.0001). While miR-let7c showed AUC = 0.7172, P = 0.0001. Our results showed that TGF-β genotypes are significantly associated with increased serum TGF-β protein levels (P < 0.0001) and reduced miR-let-7c serum levels (P < 0.0001). Bioinformatics tools confirmed that miR-let7c targets the TGF-β pathway, supporting its regulatory role. TGF-β rs 9282871 affects TGF-β production in HCC patients. The T allele, TT genotype, and downregulation of miR-let-7c activate the TGF-β pathway. Both TGF-β protein and let-7c expression can be diagnostic biomarkers of HCC. the TT genotype of the TGF-β gene can be used as a genetic biomarker for disease progression and outcome.</div> Elsevier March 2026 pdf Journal of Genetic Engineering and Biotechnology Unraveling the influence of TGF-β rs9282871 and miRNA let-7c relative expression on TGF-β production in hepatocellular carcinoma patients mixed material Elsevier