PMID- 35357586 OWN - NLM STAT- MEDLINE DCOM- 20220720 LR - 20220721 IS - 1432-1335 (Electronic) IS - 0171-5216 (Linking) VI - 148 IP - 8 DP - 2022 Aug TI - Upregulated LINC01088 facilitates malignant phenotypes and immune escape of colorectal cancer by regulating microRNAs/G3BP1/PD-L1 axis. PG - 1965-1982 LID - 10.1007/s00432-022-03981-8 [doi] AB - PURPOSE: Long intergenic non-coding RNA LINC01088 is a newly discovered long non-coding RNA (lncRNA). Its biological function in colorectal cancer (CRC) remains unknown. METHODS: Here, 36 paired CRC and para-cancerous tissues were collected. In vitro, fluorescence in situ hybridization (FISH) assay, qPCR, western blotting analysis and cellular functional experiments, RNA immunoprecipitation (RIP) assay and dual-luciferase reporter system analysis were performed. In vivo, xenograft tumor mouse models were generated. Besides, patient-derived intestinal organoid (PDO) was generated ex vivo. RESULTS: We found that LINC01088 was significantly upregulated in colorectal cancer tissues and CRC cell lines compared to adjacent normal tissues and colonic epithelial cells. High LINC01088 levels were correlated with adverse outcomes in patients with CRC. LINC01088 was mainly located in the cytoplasm. LINC01088 knockdown suppressed the proliferation, migration, invasion, and immune escape of colorectal cancer cells. Mechanistically, LINC01088 bound directly to miR-548b-5p and miR-548c-5p that were significantly upregulated Ras GTPase-activating protein-binding proteins 1 (G3BP1) and programmed death ligand 1 (PD-L1) expression, altering CRC cell phenotypes. In mouse xenograft models, LINC01088 knockdown restrained CRC tumor growth and lung metastasis. Furthermore, G3BP1 overexpression reversed LINC01088-knockdown-mediated inhibitory effects on tumor growth. Notably, LINC01088 knockdown downregulated PD-L1 expression, while G3BP1 overexpression restored PD-L1 expression in xenograft tumors. Besides, LINC01088 knockdown repressed CRC organoid growth ex vivo. CONCLUSION: Overall, these findings suggested that LINC01088 directly targeted miR-548b-5p and miR-548c-5p, promoting G3BP1 and PD-L1 expression, which facilitated colorectal cancer progression and immune escape. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Li, Chenmeng AU - Li C AD - School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. FAU - Pan, Bei AU - Pan B AD - School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. FAU - Wang, Xuhong AU - Wang X AD - School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. FAU - Liu, Xiangxiang AU - Liu X AD - School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. FAU - Qin, Jian AU - Qin J AD - School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. FAU - Gao, Tianyi AU - Gao T AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. AD - Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. FAU - Sun, Huiling AU - Sun H AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. AD - Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. FAU - Pan, Yuqin AU - Pan Y AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. panyuqin01@163.com. AD - Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. panyuqin01@163.com. FAU - Wang, Shukui AU - Wang S AUID- ORCID: 0000-0001-6972-2587 AD - School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. sk_wang@njmu.edu.cn. AD - General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. sk_wang@njmu.edu.cn. AD - Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. sk_wang@njmu.edu.cn. LA - eng GR - 81972806/National Natural Science Foundation of China/ GR - 81802093/National Natural Science Foundation of China/ GR - 82002230/National Natural Science Foundation of China/ GR - BE2019614/Jiangsu Provincial Key Research and Development Plan/ GR - LR2021017/Elderly Health Research Project of Jiangsu Province/ GR - NMUC2020035/Specialized Cohort Research Project of Nanjing Medical University/ PT - Journal Article DEP - 20220331 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (B7-H1 Antigen) RN - 0 (MIRN548 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Poly-ADP-Ribose Binding Proteins) RN - 0 (RNA Recognition Motif Proteins) RN - 0 (RNA, Long Noncoding) RN - EC 3.6.4.- (DNA Helicases) RN - EC 3.6.4.12 (G3BP1 protein, human) RN - EC 3.6.4.13 (RNA Helicases) SB - IM MH - Animals MH - B7-H1 Antigen/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - *Colorectal Neoplasms/pathology MH - DNA Helicases/genetics MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mice MH - *MicroRNAs/genetics MH - Phenotype MH - Poly-ADP-Ribose Binding Proteins/genetics MH - RNA Helicases/genetics/metabolism MH - RNA Recognition Motif Proteins/genetics/metabolism MH - *RNA, Long Noncoding/genetics OTO - NOTNLM OT - Colorectal cancer OT - Immune escape OT - LINC01088 OT - PD-L1 OT - microRNAs EDAT- 2022/04/01 06:00 MHDA- 2022/07/22 06:00 CRDT- 2022/03/31 12:06 PHST- 2022/01/13 00:00 [received] PHST- 2022/03/09 00:00 [accepted] PHST- 2022/04/01 06:00 [pubmed] PHST- 2022/07/22 06:00 [medline] PHST- 2022/03/31 12:06 [entrez] AID - 10.1007/s00432-022-03981-8 [pii] AID - 10.1007/s00432-022-03981-8 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2022 Aug;148(8):1965-1982. doi: 10.1007/s00432-022-03981-8. Epub 2022 Mar 31.