Volume 33, Issue 159 (July & August 2025)                   J Adv Med Biomed Res 2025, 33(159): 299-308 | Back to browse issues page

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Jahandoust S, Farhangiyan P, Khalili M. LincRNA-p21 Downregulation: A Suppressor of Cell Cycle Dysregulation and A Promising Biomarker for Gastric Cancer. J Adv Med Biomed Res 2025; 33 (159) :299-308
URL: http://journal.zums.ac.ir/article-1-7589-en.html
LincRNA-p21 Downregulation: A Suppressor of Cell Cycle Dysregulation and A Promising Biomarker for Gastric Cancer
Somayeh Jahandoust1 , Pourandokht Farhangiyan1 , Mitra Khalili *2
1- Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran & Department of Medical Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
2- Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran & Department of Medical Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran , khalili.mitra@gmail.com
Abstract:   (143 Views)

Background & Objective:  Gastric cancer (GC) represents a major global health concern concern, often diagnosed at advanced stages with limited effective biomarkers for early detection. Long intergenic non-coding RNA p21 (lincRNA-p21) has been implicated in many cancers, yet its role in GC is not fully understood.
 Materials & Methods:  In the current case–control design, we analyzed long intergenic non-coding RNA p21 (lincRNA-p21)  gene expression in 40 matched tumor tissues along with their adjacent non-tumor counterparts , as well as in a panel of cancer and stem-like cell lines, including GC cell lines (AGS, MKN45), esophageal adenocarcinoma cell lines (FLO-1, OE-19), the human embryonal carcinoma cell line (NTERA2), human induced pluripotent stem cells (hiPSCs), and mesenchymal stem cells (MSCs). This approach was designed to explore whether lincRNA-p21 expression is linked to stemness and tumorigenic potential. RNA was extracted and processed for cDNA preparation, followed by quantitative PCR analysis. Additionally, public TCGA data were assessed via the UALCAN platform to evaluate the expression pattern of genes critical for cell cycle control (STAT3, CDK2, E2F) in gastric adenocarcinoma samples with differing p53 mutation statuses.
Results:  A significant reduction in lincRNA-p21 expression was identified in tumor tissues compared to non-tumor samples. (P = 0.01), and its reduced expression was consistent across various malignancy grades. Similarly, GC and stem-like cell lines exhibited lower lincRNA-p21 levels compared to normal controls, suggesting a role in suppressing stemness and tumor progression. TCGA analysis revealed elevated STAT3, CDK2, and E2F expression in both p53-mutated and wild-type gastric tumors, implicating dysregulation of the lincRNA-p21–P21–P53 axis in GC pathogenesis.
Conclusion:  The reduced levels of lincRNA-p21 and P21, along with elevated STAT3, CDK2, and E2F, indicate disrupted cell cycle control and tumorigenesis in GC. Consistent lincRNA-p21 downregulation across malignancy stages suggests its potential as an early prognostic biomarker for GC detection.

Keywords: Gastric Cancer, lincRNA-p21, Cancer Stem Cells, P21-P53 Axis, Biomarker
     
Type of Study: Original Research Article | Subject: Medical Biology
Received: 2025/02/11 | Accepted: 2025/08/31 | Published: 2025/09/29
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