<i>LincRNA-p21</i> , a Potential Regulator of the Cell Cycle, Is Downregulated in Gastric Cancer

Background & Objective: Gastric cancer (GC) represents a major global health 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 the expression of lincRNA-p21 in 40 matched pairs of tumor tissues and their adjacent non-tumor counterparts, as well as in a panel of cancer and stem-like cells, including gastric (AGS, MKN45) and esophageal adenocarcinoma (FLO-1, OE-19) cell lines, the human embryonal carcinoma line (NTERA2), human induced pluripotent stem cells (hiPSCs), and mesenchymal stem cells (MSCs).This approach was designed to explore whether lincRNA-p21 expression is associated with stemness and tumorigenic potential.Total RNA was extracted, followed by cDNA synthesis and qPCR analysis.Additionally, TCGA data were assessed via the UALCAN platform to evaluate the expression pattern of key cell cycle related genes (CDKN1A, STAT3, CDK2 and E2F1) in GC samples with differing TP53 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.Likewise, GC and stem-like cell lines exhibited lower lincRNA-p21 levels relative to normal controls, suggesting a role in suppressing stemness and tumor progression.Furthermore, TCGA analysis revealed significantly elevated STAT3, CDK2, and E2F1 expression in both TP53-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, along with elevated STAT3, CDK2, and E2F1, indicate disrupted cell cycle control in GC.Consistent lincRNA-p21 downregulation across malignancy stages suggests its potential as an early prognostic biomarker for GC detection.