PMID- 36385489 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230201 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 43 IP - 2 DP - 2023 Feb TI - LINC01608 activated by YY1 facilitate hepatocellular carcinoma progression by modulating the EGFR/ERK axis. PG - 471-489 LID - 10.1111/liv.15479 [doi] AB - BACKGROUND: Long non-coding RNAs (LncRNAs) have been demonstrated to associate with a variety of cancers. However, the mechanisms of LncRNAs in hepatocellular carcinoma (HCC) progression are still not fully clarified. METHODS: LINC01608 expression level in HCC and adjacent normal tissues was detected by real-time-quantitively PCR (RT-qPCR) in clinical samples and in situ hybridization (ISH) in tissue microarray. Several functional assays were performed to determine the biological effects of LINC01608 in HCC cells in vitro, while subcutaneous xenograft models and lung metastasis models in nude mice and immunohistochemistry (IHC) results showed the role of LINC01608 in HCC progression in vivo. The combination of LINC01608 with miR-875-5p and target genes was elucidated by dual-luciferase report assays, RNA immunoprecipitation (RIP) assays and fluorescence in situ hybridization (FISH) assays. Finally, bioinformatics analysis and chromatin immunoprecipitation (CHIP) were performed to investigate the mechanism of Yin Yang-1 (YY1) regulating LINC01608 transcription. RESULTS: LINC01608 was overexpressed in HCC tissues, and high LINC01608 expression predicted poor overall survival (OS) and disease-free survival (DFS) in HCC patients. LINC01608 could promote HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated that LINC01608 could sponge to miR-875-5p and activate the EGFR/ERK pathway. Moreover, we identified transcriptional factor YY1 could bind to the promoter of LINC01608 and induce its transcription. CONCLUSION: LINC01608 could serve as a promising prognostic biomarker of HCC. YY1-activated LINC01608 could promote HCC progression by associating with miR-875-5p to induce the EGFR/ERK signalling pathway. This discovery might provide therapeutic strategies for HCC. CI - (c) 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Han, Mengzhen AU - Han M AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Liu, Furong AU - Liu F AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Li, Xinxin AU - Li X AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Zhang, Hongwei AU - Zhang H AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Pan, Yonglong AU - Pan Y AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Liu, Yachong AU - Liu Y AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Zhu, He AU - Zhu H AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Liang, Huifang AU - Liang H AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Chen, Xiaoping AU - Chen X AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Liao, Zhibin AU - Liao Z AUID- ORCID: 0000-0003-0305-2079 AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Zhang, Zhanguo AU - Zhang Z AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. FAU - Zhang, Bixiang AU - Zhang B AD - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China. LA - eng GR - 82172976/National Natural Science Foundation of China/ GR - 81502530/National Natural Science Foundation of China/ GR - 81874189/National Natural Science Foundation of China/ GR - 82103597/National Natural Science Foundation of China/ GR - [2010] 493-51/the Chinese Ministry of Public Health for Key Clinical Project/ GR - 2018ZX10723204-003/the State Key Project on Infection Disease of China/ PT - Journal Article DEP - 20221125 PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - EC 2.7.10.1 (ErbB Receptors) RN - 0 (YY1 protein, human) RN - 0 (YY1 Transcription Factor) RN - EC 2.7.10.1 (EGFR protein, human) RN - 0 (MIRN-875 microRNA, human) SB - IM MH - Animals MH - Mice MH - Humans MH - *Carcinoma, Hepatocellular/pathology MH - *Liver Neoplasms/pathology MH - *MicroRNAs/genetics MH - *RNA, Long Noncoding/genetics/metabolism MH - Mice, Nude MH - In Situ Hybridization, Fluorescence MH - Cell Line, Tumor MH - ErbB Receptors/genetics MH - YY1 Transcription Factor/genetics/therapeutic use OTO - NOTNLM OT - EGFR OT - EMT OT - YY1 OT - biomarker OT - hepatocellular carcinoma OT - long non-coding RNA EDAT- 2022/11/18 06:00 MHDA- 2023/01/25 06:00 CRDT- 2022/11/17 11:09 PHST- 2022/11/08 00:00 [revised] PHST- 2022/06/25 00:00 [received] PHST- 2022/11/12 00:00 [accepted] PHST- 2022/11/18 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2022/11/17 11:09 [entrez] AID - 10.1111/liv.15479 [doi] PST - ppublish SO - Liver Int. 2023 Feb;43(2):471-489. doi: 10.1111/liv.15479. Epub 2022 Nov 25.