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作 者:Jianjun Wang Li Zhu Quan Zhang Tian Xia Wenjian Yao Li Wei
机构地区:[1]Department of Thoracic Surgery,Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,School of Clinical Medicine,Henan University,Zhengzhou 450003,China [2]Department of Thoracic Surgery,Zhengzhou University People’s Hospital,Henan Provincial People’s Hospital,Zhengzhou 450003,China
出 处:《Acta Biochimica et Biophysica Sinica》2023年第11期1797-1805,共9页生物化学与生物物理学报(英文版)
基 金:supported by the grants from the Key Science and Technology Projects in Henan Province (Nos.202102310457 and 212102310669);the Henan Province Medical Science and Technology Research Plan Joint Construction Project (No.LHGJ20200034);the“23456 Talent Project”of Henan Provincial People’s Hospital.
摘 要: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 ex-amined.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 immuno-fluorescence(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 corre-lation with cell adhesion,ECM reconstruction,and cancer progression.LincRNA-P21 exerts its functions by nega-tively 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.
关 键 词:lincRNA-P21 esophageal squamous cell carcinoma YTHDC1 CDH5
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