Abstract：
BACKGROUND: Transmembrane protein 43 (TMEM43), a member of the transmembrane protein subfamily, plays a critical role in the initiation and development of cancers. However, little is known concerning the biological function and molecular mechanisms of TMEM43 in pancreatic cancer.
METHODS: In this study, TMEM43 expression levels were analyzed in pancreatic cancer samples compared with control samples. The relationship of TMEM43 expression and disease-free survival (DFS) and overall survival (OS) were assessed in pancreatic cancer patients. In vitro and in vivo assays were performed to explore the function and role of TMEM43 in pancreatic cancer. Coimmunoprecipitation (co-IP) followed by protein mass spectrometry was applied to analyze the molecular mechanisms of TMEM43 in pancreatic cancer.
RESULTS: We demonstrated that TMEM43 expression level is elevated in pancreatic cancer samples compared with control group, and is correlated with poor DFS and OS in pancreatic cancer patients. Knockdown of TMEM43 inhibited pancreatic cancer progression in vitro, decreased the percentage of S phase, and inhibited the tumorigenicity of pancreatic cancer in vivo. Moreover, we demonstrated that TMEM43 promoted pancreatic cancer progression by stabilizing PRPF3 and regulating the RAP2B/ERK axis.
CONCLUSIONS: The present study suggests that TMEM43 contributes to pancreatic cancer progression through the PRPF3/RAP2B/ERK axis, and might be a novel therapeutic target for pancreatic cancer.
METHODS: In this study, TMEM43 expression levels were analyzed in pancreatic cancer samples compared with control samples. The relationship of TMEM43 expression and disease-free survival (DFS) and overall survival (OS) were assessed in pancreatic cancer patients. In vitro and in vivo assays were performed to explore the function and role of TMEM43 in pancreatic cancer. Coimmunoprecipitation (co-IP) followed by protein mass spectrometry was applied to analyze the molecular mechanisms of TMEM43 in pancreatic cancer.
RESULTS: We demonstrated that TMEM43 expression level is elevated in pancreatic cancer samples compared with control group, and is correlated with poor DFS and OS in pancreatic cancer patients. Knockdown of TMEM43 inhibited pancreatic cancer progression in vitro, decreased the percentage of S phase, and inhibited the tumorigenicity of pancreatic cancer in vivo. Moreover, we demonstrated that TMEM43 promoted pancreatic cancer progression by stabilizing PRPF3 and regulating the RAP2B/ERK axis.
CONCLUSIONS: The present study suggests that TMEM43 contributes to pancreatic cancer progression through the PRPF3/RAP2B/ERK axis, and might be a novel therapeutic target for pancreatic cancer.
摘要：
背景：跨膜蛋白43（TMEM43），跨膜蛋白亚家族的一员,在癌症的发生和发展中起着至关重要的作用。然而,关于TMEM43在胰腺癌中的生物学功能和分子机制知之甚少。
方法：在本研究中，与对照样品相比,分析胰腺癌样品中的TMEM43表达水平。在胰腺癌患者中评估TMEM43表达与无病生存期（DFS）和总生存期（OS）的关系。进行体外和体内测定以探索TMEM43在胰腺癌中的功能和作用。应用免疫共沉淀（co-IP）和蛋白质质谱分析TMEM43在胰腺癌中的分子机制。
结果：我们证明，与对照组相比，胰腺癌样本中TMEM43表达水平升高，并与胰腺癌患者不良的DFS和OS相关。敲除TMEM43在体外抑制胰腺癌进展，降低了S相的百分比，并在体内抑制胰腺癌的致瘤性。此外，我们证明TMEM43通过稳定PRPF3和调节RAP2B/ERK轴促进胰腺癌进展.
结论：本研究提示TMEM43通过PRPF3/RAP2B/ERK轴促进胰腺癌进展，并可能成为胰腺癌新的治疗靶点。
方法：在本研究中，与对照样品相比,分析胰腺癌样品中的TMEM43表达水平。在胰腺癌患者中评估TMEM43表达与无病生存期（DFS）和总生存期（OS）的关系。进行体外和体内测定以探索TMEM43在胰腺癌中的功能和作用。应用免疫共沉淀（co-IP）和蛋白质质谱分析TMEM43在胰腺癌中的分子机制。
结果：我们证明，与对照组相比，胰腺癌样本中TMEM43表达水平升高，并与胰腺癌患者不良的DFS和OS相关。敲除TMEM43在体外抑制胰腺癌进展，降低了S相的百分比，并在体内抑制胰腺癌的致瘤性。此外，我们证明TMEM43通过稳定PRPF3和调节RAP2B/ERK轴促进胰腺癌进展.
结论：本研究提示TMEM43通过PRPF3/RAP2B/ERK轴促进胰腺癌进展，并可能成为胰腺癌新的治疗靶点。
