PMID- 36187110 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20221005 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Ubiquitination-mediated molecular pathway alterations in human lung squamous cell carcinomas identified by quantitative ubiquitinomics. PG - 970843 LID - 10.3389/fendo.2022.970843 [doi] LID - 970843 AB - Abnormal ubiquitination is extensively associated with cancers. To investigate human lung cancer ubiquitination and its potential functions, quantitative ubiquitinomics was carried out between human lung squamous cell carcinoma (LSCC) and control tissues, which characterized a total of 627 ubiquitin-modified proteins (UPs) and 1209 ubiquitinated lysine sites. Those UPs were mainly involved in cell adhesion, signal transduction, and regulations of ribosome complex and proteasome complex. Thirty three UPs whose genes were also found in TCGA database were significantly related to overall survival of LSCC. Six significant networks and 234 hub molecules were obtained from the protein-protein interaction (PPI) analysis of those 627 UPs. KEGG pathway analysis of those UPs revealed 47 statistically significant pathways, and most of which were tumor-associated pathways such as mTOR, HIF-1, PI3K-Akt, and Ras signaling pathways, and intracellular protein turnover-related pathways such as ribosome complex, ubiquitin-mediated proteolysis, ER protein processing, and proteasome complex pathways. Further, the relationship analysis of ubiquitination and differentially expressed proteins shows that ubiquitination regulates two aspects of protein turnover - synthesis and degradation. This study provided the first profile of UPs and molecular networks in LSCC tissue, which is the important resource to insight into new mechanisms, and to identify new biomarkers and therapeutic targets/drugs to treat LSCC. CI - Copyright (c) 2022 Zhan, Lu, Yang, Yang, Zhan, Zheng, Guo, Li, Wen, Li and Li. FAU - Zhan, Xianquan AU - Zhan X AD - Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. FAU - Lu, Miaolong AU - Lu M AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. AD - Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China. FAU - Yang, Lamei AU - Yang L AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. FAU - Yang, Jingru AU - Yang J AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. FAU - Zhan, Xiaohan AU - Zhan X AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. AD - Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China. FAU - Zheng, Shu AU - Zheng S AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. FAU - Guo, Yuna AU - Guo Y AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. FAU - Li, Biao AU - Li B AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. AD - Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China. FAU - Wen, Siqi AU - Wen S AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. AD - Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China. FAU - Li, Jiajia AU - Li J AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. AD - Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China. FAU - Li, Na AU - Li N AD - Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220915 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Ubiquitin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) RN - K3Z4F929H6 (Lysine) SB - IM MH - *Carcinoma, Non-Small-Cell Lung MH - *Carcinoma, Squamous Cell/genetics MH - Humans MH - Lung/metabolism MH - *Lung Neoplasms/genetics MH - Lysine MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proteasome Endopeptidase Complex/genetics/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - TOR Serine-Threonine Kinases/metabolism MH - Ubiquitin/metabolism MH - Ubiquitination PMC - PMC9520991 OTO - NOTNLM OT - biomarker OT - lung squamous cell carcinoma OT - signaling pathway OT - ubiquitin-proteasome system OT - ubiquitinated protein OT - ubiquitination COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/10/04 06:00 MHDA- 2022/10/05 06:00 PMCR- 2022/01/01 CRDT- 2022/10/03 04:45 PHST- 2022/06/16 00:00 [received] PHST- 2022/08/25 00:00 [accepted] PHST- 2022/10/03 04:45 [entrez] PHST- 2022/10/04 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.970843 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Sep 15;13:970843. doi: 10.3389/fendo.2022.970843. eCollection 2022.