Downregulation of miR-338-3p in Esophageal Squamous Cell Carcinoma: Diagnostic Potential and Association with Apoptotic Modulation, A Case-Control Study
نویسندگان
1 Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
2 Golestan Research Center of Gastroenterology & Hepatology (GRCGH), Golestan University of Medical Sciences, Gorgan, Iran
3 Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
4 Stem Cells and Regenerative Medicine Research Group, ACECR-Khorasan Razavi Branch, Mashhad, Iran
5 Department of Medical Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
6 Department of Biology, Faculty of Sciences, University of Birjand, Birjand, Iran
7 Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
8 Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran
9 Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
doi
10.22074/cellj.2026.2043151.1692چکیده
Objective: Delayed diagnosis of esophageal cancer (EC) contributes to its high mortality rate. The identification ofreliable diagnostic biomarkers is therefore of critical importance. MicroRNAs (miRNAs) have emerged as promisingbiomarkers detectable in both tumor tissue and circulation. In the present study, we evaluated the expression pattern ofmiR-338-3p in a population of Iranian patients with esophageal squamous cell carcinoma (ESCC).Materials and Methods: In this case-control study, formalin-fixed paraffin-embedded (FFPE) blocks of tumor specimensfrom 37 patients with ESCC, diagnosed between 2012 to 2013, were obtained from the pathology department atMashhad University of Medical Sciences and used for routine histopathological evaluation and miRNA analysis. Patientsincluded both sexes, with average age of 60.18 years old, and tumors classified to grade I–III. Paired adjacent nontumortissues served as controls. miR-338-3p expression was quantified in FFPE tissues using quantitative reversetranscription-polymerase chain reaction (qRT-PCR). For functional analysis, miR-338-3p was overexpressed in KYSE-30 cells, and cell cycle distribution and apoptosis were analyzed using flow cytometry.Results: Analysis revealed a significant downregulation of microRNA-338-3p (miR-338-3p) in 37 participants withESCC compared with adjacent non-tumor tissues (P<0.001). Receiver operating characteristic (ROC) curve analysisdemonstrated that miR-338-3p expression could discriminate tumor from non-tumor samples with an area under thecurve (AUC) of 0.8 (P<0.001), indicating acceptable diagnostic sensitivity and specificity. Functional assay in humanKYSE-30 ESCC cells showed that overexpression of miR-338-3p resulted in more than a two-fold increase in theapoptotic cell population, as measured at sub-G1 peak by flow cytometry.Conclusion: Our findings indicate that miR-338-3p is downregulated in ESCC and exhibits potential as a diagnosticbiomarker in this population of Iranian patients. Further studies are warranted to validate its clinical utility and potentialrole in targeted therapeutic strategies.
