机构：[1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[2]Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.[3]Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy.[4]Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
Glycosylation is crucial for the stability and biological functions of proteins. The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. However, the functions of STT3A in LUAD are still unclear.The expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. STT3A was knocked-out using CRISPR/Cas9 and inhibited by NGI-1. Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot.The expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. The high expression of STT3A was significantly associated with poor OS in LUAD patients. The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. Similarly, the knockout or inhibition of STT3A suppressed tumor growth in vivo. In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition.STT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients.2022 Translational Lung Cancer Research. All rights reserved.
基金：
This research was funded by the National Natural Science Foundation of China (No. 31771549 to Y Chen) and Key Projects of Sichuan Province (No. 2021YFS0233 and No. 2021-YF05-00751-SN to J Cheng). This work was also supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYGD18021 to L Liu)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|3 区呼吸系统4 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|3 区肿瘤学3 区呼吸系统
第一作者：
第一作者机构：[1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.[*1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, China
推荐引用方式(GB/T 7714)：
Cheng Jiahan,Xia Liang,Hao Xiaohu,et al.Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway[J].Translational lung cancer research.2022,11(6):1089-1107.doi:10.21037/tlcr-22-396.
APA：
Cheng Jiahan,Xia Liang,Hao Xiaohu,Gan Fanyi,Bai Yuquan...&Liu Lunxu.(2022).Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway.Translational lung cancer research,11,(6)
MLA：
Cheng Jiahan,et al."Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway".Translational lung cancer research 11..6(2022):1089-1107
