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Journal of Cancer Research and Clinical Oncology

Erschienen in:

31.03.2022 | Original Article – Cancer Research

Upregulated LINC01088 facilitates malignant phenotypes and immune escape of colorectal cancer by regulating microRNAs/G3BP1/PD-L1 axis

verfasst von: Chenmeng Li, Bei Pan, Xuhong Wang, Xiangxiang Liu, Jian Qin, Tianyi Gao, Huiling Sun, Yuqin Pan, Shukui Wang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2022

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Abstract

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.

Nur mit Berechtigung zugänglich

Ai H, Xie W, Xiu AH, Li N, Zhang ST, Zhang YL, Xue XO (2018) The down-regulation of long non-coding RNA LINC01088 is associated with the poor prognosis of epithelial ovarian cancer patients. Eur Rev Med Pharmacol Sci 22:5836–5841PubMed

Anania G, Resta G, Marino S, Fabbri N, Scagliarini L, Marchitelli I, Fiorica F, Cavallesco G (2019) Treatment of colorectal cancer: a multidisciplinary approach. J Gastrointest Cancer 50:458–468PubMedCrossRef

Antonangeli F, Natalini A, Garassino MC, Sica A, Santoni A, Di Rosa F (2020) Regulation of PD-L1 expression by NF-κB in cancer. Front Immunol 11:584626PubMedPubMedCentralCrossRef

Castellano JJ, Navarro A, Viñolas N, Marrades RM, Moises J, Cordeiro A, Saco A, Muñoz C, Fuster D, Molins L et al (2016) LincRNA-p21 impacts prognosis in resected non-small cell lung cancer patients through angiogenesis regulation. J Thoracic Oncol 11:2173–2182CrossRef

Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB (2019) Colorectal cancer. Lancet (london, England) 394:1467–1480CrossRef

Dykes IM, Emanueli C (2017) Transcriptional and Post-transcriptional gene regulation by long non-coding RNA. Genom Proteom Bioinform 15:177–186CrossRef

Fang Y, Fullwood MJ (2016) Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genom Proteom Bioinform 14:42–54CrossRef

Franke AJ, Skelton WP, Starr JS, Parekh H, Lee JJ, Overman MJ, Allegra C, George TJ (2019) Immunotherapy for colorectal cancer: a review of current and novel therapeutic approaches. J Natl Cancer Inst 111:1131–1141PubMedPubMedCentralCrossRef

Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034PubMedPubMedCentralCrossRef

Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719PubMedPubMedCentralCrossRef

Jahangiri A, Dadmanesh M, Ghorban K (2020) STAT3 inhibition reduced PD-L1 expression and enhanced antitumor immune responses. J Cell Physiol 235:9457–9463PubMedCrossRef

Li B, Severson E, Pignon JC, Zhao H, Li T, Novak J, Jiang P, Shen H, Aster JC, Rodig S et al (2016) Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol 17:174PubMedPubMedCentralCrossRef

Li C, Pan B, Liu X, Qin J, Wang X, He B, Pan Y, Sun H, Xu T, Xu X et al (2021a) Long intergenic non-coding RNA LINC00485 exerts tumor-suppressive activity by regulating miR-581/EDEM1 axis in colorectal cancer. Aging 13:3866–3885PubMedPubMedCentralCrossRef

Li L, Zhang X, Liu N, Chen X, Peng C (2021b) LINC00473: A novel oncogenic long noncoding RNA in human cancers. J Cell Physiol 236:4174–4183PubMedCrossRef

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B, Liu XS (2017) TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Can Res 77:e108–e110CrossRef

Liu J, Yao Y, Hu Z, Zhou H, Zhong M (2019a) Transcriptional profiling of long-intergenic noncoding RNAs in lung squamous cell carcinoma and its value in diagnosis and prognosis. Mol Genet Genom Med 7:e994

Liu JQ, Feng YH, Zeng S, Zhong MZ (2020) linc01088 promotes cell proliferation by scaffolding EZH2 and repressing p21 in human non-small cell lung cancer. Life Sci 241:117134PubMedCrossRef

Liu Y, Cao X (2016) Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med (berlin, Germany) 94:509–522CrossRef

Liu ZS, Cai H, Xue W, Wang M, Xia T, Li WJ, Xing JQ, Zhao M, Huang YJ, Chen S et al (2019b) G3BP1 promotes DNA binding and activation of cGAS. Nat Immunol 20:18–28PubMedCrossRef

Nappi A, Berretta M, Romano C, Tafuto S, Cassata A, Casaretti R, Silvestro L, Divitiis C, Alessandrini L, Fiorica F et al (2018) Metastatic colorectal cancer: role of target therapies and future perspectives. Curr Cancer Drug Targets 18:421–429PubMedCrossRef

Nguyen LH, Goel A, Chung DC (2020) Pathways of colorectal carcinogenesis. Gastroenterology 158:291–302PubMedCrossRef

Novikov NM, Zolotaryova SY, Gautreau AM, Denisov EV (2021) Mutational drivers of cancer cell migration and invasion. Br J Cancer 124:102–114PubMedCrossRef

Omer A, Barrera MC, Moran JL, Lian XJ, Di Marco S, Beausejour C, Gallouzi IE (2020) G3BP1 controls the senescence-associated secretome and its impact on cancer progression. Nat Commun 11:4979PubMedPubMedCentralCrossRef

Palazzo AF, Koonin EV (2020) Functional long non-coding RNAs evolve from junk transcripts. Cell 183:1151–1161PubMedCrossRef

Pan Y, Liang W, Zhao X, Liu L, Qing Y, Li Y (2016) miR-548b inhibits the proliferation and invasion of malignant gliomas by targeting metastasis tumor-associated protein-2. NeuroReport 27:1266–1273PubMedCrossRef

Picard E, Verschoor CP, Ma GW, Pawelec G (2020) Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer. Front Immunol 11:369PubMedPubMedCentralCrossRef

Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47–62PubMedCrossRef

Ransohoff JD, Wei Y, Khavari PA (2018) The functions and unique features of long intergenic non-coding RNA. Nat Rev Mol Cell Biol 19:143–157PubMedCrossRef

Reisländer T, Groelly FJ, Tarsounas M (2020) DNA damage and cancer immunotherapy: a STING in the tale. Mol Cell 80:21–28PubMedCrossRef

Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T (2018) Emerging roles of long non-coding RNA in cancer. Cancer Sci 109:2093–2100PubMedPubMedCentralCrossRef

Schmitz SU, Grote P, Herrmann BG (2016) Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci 73:2491–2509PubMedPubMedCentralCrossRef

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin 71:209–249CrossRef

Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154:26–46PubMedPubMedCentralCrossRef

Van Cutsem E, Cervantes A, Nordlinger B, Arnold D (2014) Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):1–9

Wang Z, Wu X, Hou X, Zhao W, Yang C, Wan W, Chen L (2020) miR-548b-3p functions as a tumor suppressor in lung cancer. Lasers Med Sci 35:833–839PubMedCrossRef

Xu Y, Zhong YD, Zhao XX (2020) MiR-548b suppresses proliferative capacity of colorectal cancer by binding WNT2. Eur Rev Med Pharmacol Sci 24:10535–10541PubMed

Xu M, Xu X, Pan B, Chen X, Lin K, Zeng K, Liu X, Xu T, Sun L, Qin J et al (2019) LncRNA SATB2-AS1 inhibits tumor metastasis and affects the tumor immune cell microenvironment in colorectal cancer by regulating SATB2. Mol Cancer 18:135PubMedPubMedCentralCrossRef

Yan Y, Ren L, Liu Y, Liu L (2021) Long non-coding RNA CRNDE as potential biomarkers facilitate inflammation and apoptosis in alcoholic liver disease. Aging 13:23233–23244PubMedPubMedCentralCrossRef

Yeung KT, Yang J (2017) Epithelial-mesenchymal transition in tumor metastasis. Mol Oncol 11:28–39PubMedCrossRef

You J, Li J, Ke C, Xiao Y, Lu C, Huang F, Mi Y, Xia R, Li Q (2021) Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer. Oncogene 40:4151–4166PubMedPubMedCentralCrossRef

Zhang CH, Wang JX, Cai ML, Shao R, Liu H, Zhao WL (2019) The roles and mechanisms of G3BP1 in tumour promotion. J Drug Target 27:300–305PubMedCrossRef

Zhang W, Fei J, Yu S, Shen J, Zhu X, Sadhukhan A, Lu W, Zhou J (2018) LINC01088 inhibits tumorigenesis of ovarian epithelial cells by targeting miR-24-1-5p. Sci Rep 8:2876PubMedPubMedCentralCrossRef

Zhao H, Li Y, Dong N, Zhang L, Chen X, Mao H, Al-Ameri SAA, Wang X, Wang Q, Du L et al (2021) LncRNA LINC01088 inhibits the function of trophoblast cells, activates the MAPK-signaling pathway and associates with recurrent pregnancy loss. Mol Hum Reprod. https://doi.org/10.1093/molehr/gaab047CrossRefPubMedPubMedCentral

Zhou T, Lin K, Nie J, Pan B, He B, Pan Y, Sun H, Xu T, Wang S (2021) LncRNA SPINT1-AS1 promotes breast cancer proliferation and metastasis by sponging let-7 a/b/i-5p. Pathol Res Pract 217:153268PubMedCrossRef

Titel: Upregulated LINC01088 facilitates malignant phenotypes and immune escape of colorectal cancer by regulating microRNAs/G3BP1/PD-L1 axis
verfasst von: Chenmeng Li
Bei Pan
Xuhong Wang
Xiangxiang Liu
Jian Qin
Tianyi Gao
Huiling Sun
Yuqin Pan
Shukui Wang
Publikationsdatum: 31.03.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2022
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-022-03981-8

Springer Medizin

Upregulated LINC01088 facilitates malignant phenotypes and immune escape of colorectal cancer by regulating microRNAs/G3BP1/PD-L1 axis