Long non-coding RNA CCDC183-AS1 acts AS a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression
Tóm tắt
Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined.
Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1.
Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC.
CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.
Từ khóa
Tài liệu tham khảo
Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ, Ning S, Deng Y, Zhao J, Jiang S, Yuan Y, et al. TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012;22:291–303.
Shao RX, Otsuka M, Kato N, Taniguchi H, Hoshida Y, Moriyama M, Kawabe T, Omata M. Acyclic retinoid inhibits human hepatoma cell growth by suppressing fibroblast growth factor-mediated signaling pathways. Gastroenterology. 2005;128:86–95.
Fang JH, Xu L, Shang LR, Pan CZ, Ding J, Tang YQ, Liu H, Liu CX, Zheng JL, Zhang YJ, et al. Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma. Hepatology. 2019;70:824–39.
Chen T, Dai X, Dai J, Ding C, Zhang Z, Lin Z, Hu J, Lu M, Wang Z, Qi Y, et al. AFP promotes HCC progression by suppressing the HuR-mediated Fas/FADD apoptotic pathway. Cell Death Dis. 2020;11:822.
DiDonato JA, Mercurio F, Karin M. NF-κB and the link between inflammation and cancer. Immunol Rev. 2012;246:379–400.
Böttcher K, Pinzani M. Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents. Adv Drug Deliv Rev. 2017;121:3–8.
Lisker-Melman M, Jonnalagadda S. Swimming in cloudy waters: efforts to prevent HCV-related HCC. Gastroenterology. 2005;129:1794–6.
Hyun MH, Lee YS, Kim JH, Lee CU, Jung YK, Seo YS, Yim HJ, Yeon JE, Byun KS. Hepatic resection compared to chemoembolization in intermediate- to advanced-stage hepatocellular carcinoma: A meta-analysis of high-quality studies. Hepatology. 2018;68:977–93.
Carotenuto P, Fassan M, Pandolfo R, Lampis A, Vicentini C, Cascione L, Paulus-Hock V, Boulter L, Guest R, Quagliata L, et al. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut. 2017;66:1268–77.
Hardy T, Mann DA. Epigenetics in liver disease: from biology to therapeutics. Gut. 2016;65:1895–905.
Sherpa C, Rausch JW, Le Grice SF. Structural characterization of maternally expressed gene 3 RNA reveals conserved motifs and potential sites of interaction with polycomb repressive complex 2. Nucleic Acids Res. 2018;46:10432–10447.
Xing Z, Lin A, Li C, Liang K, Wang S, Liu Y, Park PK, Qin L, Wei Y, Hawke DH, et al. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell. 2014;159:1110–25.
Militello G, Weirick T, John D, Döring C, Dimmeler S, Uchida S. Screening and validation of lncRNAs and circRNAs as miRNA sponges. Brief Bioinform. 2017 Sep 1;18(5):780–8.
Bai Y, Long J, Liu Z, Lin J, Huang H, Wang D, Yang X, Miao F, Mao Y, Sang X, et al. Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression. J Cell Physiol. 2019;234:18837–48.
Li B, Mao R, Liu C, Zhang W, Tang Y, Guo Z. LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. Life Sci. 2018;197:122–9.
Fan H, Lv P, Mu T, Zhao X, Liu Y, Feng Y, Lv J, Liu M, Tang H. LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells. Cancer Lett. 2018;429:89–99.
Liu F, Qin L, Liao Z, Song J, Yuan C, Liu Y, Wang Y, Xu H, Zhang Q, Pei Y, et al. Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma. Exp Hematol Oncol. 2020;9:10.
Rashid F, Shah A, Shan G. Long Non-coding RNAs in the Cytoplasm. Genomics Proteomics Bioinformatics. 2016;14:73–80.
Dykes IM, Emanueli C. Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA. Genomics Proteomics Bioinformatics. 2017;15:177–86.
Paraskevopoulou MD, Vlachos IS, Karagkouni D, Georgakilas G, Kanellos I, Vergoulis T, Zagganas K, Tsanakas P, Floros E, Dalamagas T, et al. DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts. Nucleic Acids Res. 2016;44:D231–8.
Leitão AL, Costa MC. Enguita FJ. A guide for miRNA target prediction and analysis using web-based applications. Methods Mol Biol. 2014;1182:265–77.
Paraskevopoulou MD, Georgakilas G, Kostoulas N, Vlachos IS, Vergoulis T, Reczko M, Filippidis C, Dalamagas T, Hatzigeorgiou AG. DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res. 2013;41:W169–73.
Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife. 2015;4:e05005.
Dweep H, Gretz N. miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 2015;12:697.
Wang X, El Naqa IM. Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics. 2008;24:325–32.
Lim LJ, Wong S, Huang F, Lim S, Chong SS, Ooi LL, Kon OL, Roles LCG. Regulation of Long Noncoding RNAs in Hepatocellular Carcinoma. Cancer Res. 2019;79:5131–9.
Fang Y, Roles FMJ. Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genomics Proteomics Bioinformatics. 2016;14:42–54.
Feng J, Yang G, Liu Y, Gao Y, Zhao M, Bu Y, Yuan H, Yuan Y, Yun H, Sun M, et al. LncRNA PCNAP1 modulates hepatitis B virus replication and enhances tumor growth of liver cancer. Theranostics. 2019;9:5227–45.
Zhang J, Li Z, Liu L, Wang Q, Li S, Chen D, Hu Z, Yu T, Ding J, Li J, et al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology. 2018;67:171–87.
Kang CL, Qi B, Cai QQ, Fu LS, Yang Y, Tang C, Zhu P, Chen QW, Pan J, Chen MH, et al. LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics. 2019;9:4421–36.
Wang Y, Yang L, Chen T, Liu X, Guo Y, Zhu Q, Tong X, Yang W, Xu Q, Huang D, et al. A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol Cancer. 2019;18:28.
Klingenberg M, Matsuda A, Diederichs S, Patel T. Non-coding RNA in hepatocellular carcinoma: Mechanisms. biomarkers and therapeutic targets. J Hepatol. 2017;67:603–18.
Zhu Q, Luo Z, Lu G, Gui F, Wu J, Li F, Ni Y. LncRNA FABP5P3/miR-589-5p/ZMYND19 axis contributes to hepatocellular carcinoma cell proliferation, migration and invasion. Biochem Biophys Res Commun. 2018;498:551–8.
Zhang X, Jiang P, Shuai L, Chen K, Li Z, Zhang Y, Jiang Y, Li X. miR-589-5p inhibits MAP3K8 and suppresses CD90+ cancer stem cells in hepatocellular carcinoma. J Exp Clin Cancer Res. 2016;35:176.
Long J, Jiang C, Liu B, Dai Q, Hua R, Chen C, Zhang B, Li H. Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes chemoresistance via STAT3 signaling. Cancer Lett. 2018;423:113–26.
Xu M, Wang Y, He HT, Yang Q. MiR-589-5p is a potential prognostic marker of hepatocellular carcinoma and regulates tumor cell growth by targeting MIG-6. Neoplasma. 2018;65:753–61.
Guan Y, Leu NA, Ma J, Chmátal L, Ruthel G, Bloom JC, Lampson MA, Schimenti JC, Luo M, Wang PJ. SKP1 drives the prophase I to metaphase I transition during male meiosis. Sci Adv. 2020;6:eaaz2129.
Dang F, Nie L, Wei W. Ubiquitin signaling in cell cycle control and tumorigenesis. Cell Death Differ. 2020.
Jang SM, Redon CE, Thakur BL, Bahta MK, Aladjem MI. Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases. Exp Mol Med. 2020;52:1637–51.
Nogueira V, Sundararajan D, Kwan JM, Peng XD, Sarvepalli N, Sonenberg N, Hay N. Akt-dependent Skp2 mRNA translation is required for exiting contact inhibition, oncogenesis. and adipogenesis. EMBO J. 2012;31:1134–46.