PMID- 35069968 OWN - NLM STAT- MEDLINE DCOM- 20220307 LR - 20220307 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2021 DP - 2021 TI - LYAR Promotes Colorectal Cancer Progression by Upregulating FSCN1 Expression and Fatty Acid Metabolism. PG - 9979707 LID - 10.1155/2021/9979707 [doi] LID - 9979707 AB - Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, is expressed at a higher level in CRC tissue than in adjacent normal tissue and that LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells in vitro, but knockdown (KD) of LYAR in CRC cells also inhibits xenograft tumor metastasis in vivo. Microarray analysis of LYAR KD cells combined with a chromatin immunoprecipitation (ChIP) assay, gene reporter assay, and rescue experiment indicated that FSCN1 (encoding fascin actin-bundling protein 1 (Fascin-1)) serves as a novel key regulator of LYAR-promoted migration and invasion of CRC cells. Knockdown of FSCN1 significantly inhibits subcutaneous tumorigenesis of CRC cells and leads to the downregulation of FASN and SCD, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by upregulating FSCN1 expression and affecting fatty acid metabolism in CRC. CI - Copyright (c) 2021 Yupeng Wu et al. FAU - Wu, Yupeng AU - Wu Y AUID- ORCID: 0000-0003-4451-9739 AD - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Zhou, Yu AU - Zhou Y AD - Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215000, China. FAU - Gao, Haiying AU - Gao H AD - School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, China. FAU - Wang, Yajun AU - Wang Y AD - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Cheng, Qingyu AU - Cheng Q AD - MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China. FAU - Jian, Shikun AU - Jian S AD - MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China. FAU - Ding, Qi AU - Ding Q AD - School of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Gu, Wei AU - Gu W AD - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Yao, Yanxue AU - Yao Y AD - School of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Ma, Jia AU - Ma J AD - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Wu, Wenjuan AU - Wu W AD - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Li, Yuyun AU - Li Y AD - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Tong, Xuhui AU - Tong X AD - School of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, China. FAU - Song, Xiaoyuan AU - Song X AUID- ORCID: 0000-0002-9011-5033 AD - MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China. FAU - Ma, Sai AU - Ma S AUID- ORCID: 0000-0002-0863-4724 AD - Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215000, China. LA - eng PT - Journal Article DEP - 20211206 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Carrier Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (FSCN1 protein, human) RN - 0 (Fatty Acids) RN - 0 (LYAR protein, human) RN - 0 (Microfilament Proteins) RN - 0 (Nuclear Proteins) RN - 146808-54-0 (fascin) SB - IM MH - Animals MH - Carrier Proteins/*metabolism MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Colorectal Neoplasms/*genetics/metabolism MH - DNA-Binding Proteins/*metabolism MH - Fatty Acids/*metabolism MH - Female MH - Humans MH - Mice MH - Mice, Inbred NOD MH - Microfilament Proteins/*metabolism MH - Nuclear Proteins/*metabolism MH - Transfection MH - Up-Regulation PMC - PMC8769847 COIS- The authors declare no conflict of interest. EDAT- 2022/01/25 06:00 MHDA- 2022/03/08 06:00 PMCR- 2021/12/06 CRDT- 2022/01/24 08:50 PHST- 2021/07/16 00:00 [received] PHST- 2021/11/05 00:00 [revised] PHST- 2021/11/12 00:00 [accepted] PHST- 2022/01/24 08:50 [entrez] PHST- 2022/01/25 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2021/12/06 00:00 [pmc-release] AID - 10.1155/2021/9979707 [doi] PST - epublish SO - Oxid Med Cell Longev. 2021 Dec 6;2021:9979707. doi: 10.1155/2021/9979707. eCollection 2021.