Dysregulation of circ-SMARCA5, circ-RHOT1, and HNF1A and the association of HNF1A polymorphisms with hepatocellular carcinoma.

Authors

Basma A Ibrahim, Basma S Elsayed, Mohamed Abdelaziz Gendia, Manar Moustafa, Ansam M Z El Desoky

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 28, 2026. Epub Aug 28, 2026.

Abstract

Hepatocellular carcinoma (HCC) accounts for many cancer-related morbidity and mortality cases. This study aimed to assess the expression of circ-SMARCA5, circ-RHOT1, and hepatocyte nuclear factor 1 homeobox A (HNF1A). Analyze the protein expression of HNF1A, and identify HNF1A polymorphism and its correlation with HCC incidence and staging.
In this study, 48 HCC patients and 48 age-matched controls were selected. The expressions of circ-SMARCA5, circ-RHOT1, and HNF1A were determined using qRT-PCR in paired HCC and adjacent non-neoplastic liver tissues. HNF1A rs2464196 and rs1169310 polymorphisms were genotyped using TaqMan assays, while serum AFP concentrations were measured by ELISA.
GA and AA genotypes of rs2464196 were more frequent among HCC cases and were associated with higher odds of HCC compared with the GG genotype, while CT and TT genotypes of rs1169310 were associated with higher risk compared to CC genotype. Also, A allele of rs2464196 and T allele of rs1169310 were more prevalent in patients with HCC. Circ-SMARCA5 and HNF1A expressions were significantly downregulated, whereas circ-RHOT1 expression was significantly upregulated in tumor tissues compared to adjacent non-neoplastic tissue (P < 0.001 for all). Circ-SMARCA5 and HNF1A expressions were correlated with lower serum AFP level, while circ-RHOT1 expression correlated with higher serum AFP. Lower circ-SMARCA5 and HNF1A expressions, and higher circ-RHOT1 expression were associated with advanced BCLC stage. Immunohistochemical staining showed reduced nuclear HNF1A expression in HCC tissues, which was associated with advanced BCLC stage and HNF1A variant genotypes.
The association between HNF1A rs2464196 and rs1169310 genotypes and HCC susceptibility was found in the studied Egyptian population. Dysregulation of circ-SMARCA5, circ-RHOT1 and HNF1A expression, as well as reduced HNF1A protein expression were associated with HCC development and more advanced disease.

PMID:
42663735
Bibliographic data and abstract were imported from PubMed on 29 Aug 2026.

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