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miR-199a-3p promotes gastric cancer progression by promoting its stemness potential via DDR2 mediation

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机构： [1]Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [2]Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [3]Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [4]Inflammation and Allergic Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [5]Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany [6]Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Str. 36, Munich 80336, Germany

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Peritoneal metastasis (PM) is an independent prognostic factor in gastric cancer (GC), however, the underlying mechanisms of PM occurrence remain unclear.The roles of DDR2 were investigated in GC and its potential relationship to PM, and orthotopic implants into nude mice were performed to assess the biological effects of DDR2 on PM.Herein, DDR2 level is more significantly observed to elevate in PM lesion than the primary lesion. GC with DDR2-high expression evokes a worse overall survival (OS) in TCGA, similar results of the gloomy OS with high DDR2 levels are clarified via the stratifying stage of TNM. The conspicuously increased expression of DDR2 was found in GC cell lines, luciferase reporter assays verified that miR-199a-3p directly targeted DDR2 gene, which was correlated to tumor progression. We ulteriorly observed DDR2 participated in GC stemness maintenance via mediating pluripotency factor SOX2 expression and implicated in autophagy and DNA damage of cancer stem cells (CSCs). In particular, DDR2 dominated EMT programming through recruiting NFATc1-SOX2 complex to Snai1 in governing cell progression, controlling by DDR2-mTOR-SOX2 axis in SGC-7901 CSCs. Furthermore, DDR2 promoted the tumor peritoneal dissemination in gastric xenograft mouse model.Phenotype screens and disseminated verifications incriminating in GC exposit the miR-199a-3p-DDR2-mTOR-SOX2 axis as a clinically actionable target for tumor PM progression. The herein-reported DDR2-based underlying axis in GC represents novel and potent tools for studying the mechanisms of PM.Copyright © 2023 Elsevier Inc. All rights reserved.

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出版当年[2023]版：

大类 | 2 区生物学

小类 | 3 区细胞生物学

最新[2023]版：

大类 | 2 区生物学

小类 | 3 区细胞生物学

第一作者：

第一作者机构： [1]Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [5]Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany

通讯作者：

通讯机构： [2]Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [4]Inflammation and Allergic Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China [6]Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Str. 36, Munich 80336, Germany [*1]Taiping Str. 25, Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

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