LincRNA-P21 knockdown facilitates esophageal squamous cell carcinoma cell progression by upregulating cadherin 5 via YTH domain containing 1.

LincRNA-P21 is a tumor suppressor in esophageal squamous cell carcinoma (ESCC). Cell adhesion modules play vital roles in cell-cell and cell-extracellular matrix (ECM) interactions and malignant cancer progression. In this study, we investigate whether lincRNA-P21 exerts its functions by regulating the cell adhesion molecule cadherin 5 (CDH5) in ESCC. Moreover, the RNA binding protein (RBP) mediators of lincRNA-P21 and CDH5 are further examined. Cell viability, growth and migratory ability are assessed by calcein-AM/PI double staining, CCK-8, EdU, Transwell, and wound healing assays. The expression of collagen I and fibronectin is examined by immunofluorescence (IF). LincRNA-P21 and CDH5 are quantified by RT-qPCR and western blot analysis. Potential lincRNA-P21 targets are identified by RNA sequencing. RBPs that can interact with lincRNA-P21 and CDH5 are identified by RNA immunoprecipitation (RIP) assay. LincRNA-P21 knockdown increases cell viability, growth, cell migration, and collagen I and fibronectin expression in ESCC cells. LincRNA-P21 depletion induces the dysregulation of 316 genes, including CDH5, in TE-1 cells. CDH5 is identified as a downstream molecule of lincRNA-P21 given its close correlation with cell adhesion, ECM reconstruction, and cancer progression. LincRNA-P21 exerts its functions by negatively regulating CDH5 expression. YTH domain containing 1 (YTHDC1) mediates the regulatory effect of lincRNA-P21 on CDH5. LincRNA-P21 knockdown elevates cell viability and growth, promotes cell migration, and induces ECM reorganization by upregulating CDH5 via RBP YTHDC1 in ESCC.

Citation

Jianjun Wang, Li Zhu, Quan Zhang, Tian Xia, Wenjian Yao, Li Wei. LincRNA-P21 knockdown facilitates esophageal squamous cell carcinoma cell progression by upregulating cadherin 5 via YTH domain containing 1. Acta biochimica et biophysica Sinica. 2023 Nov 25;55(11):1797-1805

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PMID: 37766459

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