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Journal of Cancer Research and Clinical Oncology

Erschienen in:

26.06.2019 | Original Article – Cancer Research

A liver-specific lncRNA, FAM99B, suppresses hepatocellular carcinoma progression through inhibition of cell proliferation, migration, and invasion

verfasst von: Meile Mo, Shun Liu, Xiaoyun Ma, Chao Tan, Liangjia Wei, Yonghong Sheng, Yanye Song, Xiaoyun Zeng, Dongping Huang, Xiaoqiang Qiu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2019

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Abstract

Background

Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important in hepatocellular carcinoma (HCC) development and progression. In this study, we aim to evaluate the expression of lncRNA FAM99B and its biological function in HCC.

Methods

The expression level of FAM99B in HCC was assessed based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), verified using quantitative real-time polymerase chain reaction (qRT-PCR). HCCLM3 was transfected with lentivirus containing full-length FAM99B to obtain stable overexpressing cell line. Cell Counting Kit 8, clone formation, and transwell assays were used to investigate the effects of FAM99B in HCC progression. In addition, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PANTHER pathway analyses were conducted to investigate the underlying molecular mechanisms.

Results

FAM99B was found to be downregulated in HCC tissues compared with adjacent normal tissues based on TCGA, GEO, and qRT-PCR data. Our results revealed that downregulated FAM99B was significantly associated with vascular invasion, advanced histologic grade, and T stage. Kaplan–Meier analysis using TCGA data indicated that decreased FAM99B levels were significantly associated with poor overall survival in patients with HCC. Moreover, overexpression of FAM99B significantly inhibited cell proliferation, migration, and invasion in vitro. Pathway analyses showed that the co-expressed genes of FAM99B mainly participated in the pathways “Metabolic pathways” and “Blood coagulation”.

Conclusion

Our results suggest that FAM99B may serve as a tumor suppressor in HCC and may provide a promising therapy target for patients with HCC.

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Adler P, Kolde R, Kull M, Tkachenko A, Peterson H, Reimand J, Vilo J (2009) Mining for coexpression across hundreds of datasets using novel rank aggregation and visualization methods. Genome Biol 10:R139. https://doi.org/10.1186/gb-2009-10-12-r139 CrossRefPubMedPubMedCentral

Atanasovska B et al (2017) A liver-specific long noncoding RNA with a role in cell viability is elevated in human nonalcoholic steatohepatitis. Hepatology 66:794–808. https://doi.org/10.1002/hep.29034 CrossRefPubMed

Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed

Boccaccio C, Medico E (2006) Cancer and blood coagulation. Cell Mol Life Sci 63:1024–1027. https://doi.org/10.1007/s00018-005-5570-9 CrossRefPubMed

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492 CrossRefPubMed

Cerami E et al (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404. https://doi.org/10.1158/2159-8290.CD-12-0095 CrossRefPubMed

Chang J et al (2004) miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 1:106–113CrossRefPubMed

DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20. https://doi.org/10.1016/j.cmet.2007.10.002 CrossRefPubMed

DerSimonian R, Laird N (2015) Meta-analysis in clinical trials revisited. Contemp Clin Trials 45:139–145. https://doi.org/10.1016/j.cct.2015.09.002 CrossRefPubMedPubMedCentral

Fagerberg L et al (2014) Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteom 13:397–406. https://doi.org/10.1074/mcp.M113.035600 CrossRef

Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. Lancet 391:1301–1314. https://doi.org/10.1016/S0140-6736(18)30010-2 CrossRefPubMed

Gao J et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6:l1. https://doi.org/10.1126/scisignal.2004088 CrossRef

Ge Z et al (2017) Long noncoding RNA SchLAH suppresses metastasis of hepatocellular carcinoma through interacting with fused in sarcoma. Cancer Sci 108:653–662. https://doi.org/10.1111/cas.13200 CrossRefPubMedPubMedCentral

Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719. https://doi.org/10.4161/rna.20481 CrossRefPubMedPubMedCentral

He Y, Meng XM, Huang C, Wu BM, Zhang L, Lv XW, Li J (2014) Long noncoding RNAs: novel insights into hepatocelluar carcinoma. Cancer Lett 344:20–27. https://doi.org/10.1016/j.canlet.2013.10.021 CrossRefPubMed

He J et al (2019) A novel, liver-specific long noncoding RNA LINC01093 suppresses HCC progression by interaction with IGF2BP1 to facilitate decay of GLI1 mRNA. Cancer Lett 450:98–109. https://doi.org/10.1016/j.canlet.2019.02.033 CrossRefPubMed

Huang S, He X (2011) The role of microRNAs in liver cancer progression. Br J Cancer 104:235–240. https://doi.org/10.1038/sj.bjc.6606010 CrossRefPubMed

Kessler SM et al (2014) Fatty acid elongation in non-alcoholic steatohepatitis and hepatocellular carcinoma. Int J Mol Sci 15:5762–5773. https://doi.org/10.3390/ijms15045762 CrossRefPubMedPubMedCentral

Lanzafame M, Bianco G, Terracciano LM, Ng CKY, Piscuoglio S (2018) The role of long non-coding RNAs in hepatocarcinogenesis. Int J Mol Sci. https://doi.org/10.3390/ijms19030682 CrossRefPubMedPubMedCentral

Lee GL, Dobi A, Srivastava S (2011) Prostate cancer: diagnostic performance of the PCA3 urine test. Nat Rev Urol 8:123–124. https://doi.org/10.1038/nrurol.2011.10 CrossRefPubMed

Li J et al (2015) TANRIC: an interactive open platform to explore the function of lncRNAs in cancer. Cancer Res 75:3728–3737. https://doi.org/10.1158/0008-5472.can-15-0273 CrossRefPubMedPubMedCentral

Liu J, Lu C, Xiao M, Jiang F, Qu L, Ni R (2017) Long non-coding RNA SNHG20 predicts a poor prognosis for HCC and promotes cell invasion by regulating the epithelial-to-mesenchymal transition. Biomed Pharmacother 89:857–863. https://doi.org/10.1016/j.biopha.2017.01.011 CrossRefPubMed

Ni W et al (2017) A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1. J Hematol Oncol 10:91. https://doi.org/10.1186/s13045-017-0449-4 CrossRefPubMedPubMedCentral

Sciacovelli M, Frezza C (2017) Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer. FEBS J 284:3132–3144. https://doi.org/10.1111/febs.14090 CrossRefPubMedPubMedCentral

Sun QM et al (2018) Long non-coding RNA00607 as a tumor suppressor by modulating NF-kappaB p65/p53 signaling axis in hepatocellular carcinoma. Carcinogenesis. https://doi.org/10.1093/carcin/bgy113 CrossRefPubMedPubMedCentral

Vander Heiden MG et al (2011) Metabolic pathway alterations that support cell proliferation. Cold Spring Harb Symp Quant Biol 76:325–334. https://doi.org/10.1101/sqb.2012.76.010900 CrossRefPubMed

Wan HG, Xu H, Gu YM, Wang H, Xu W, Zu MH (2014) Comparison osteopontin vs AFP for the diagnosis of HCC: a meta-analysis. Clin Res Hepatol Gastroenterol 38:706–714. https://doi.org/10.1016/j.clinre.2014.06.008 CrossRefPubMed

Wang HP, Rogler CE (1988) Deletions in human chromosome arms 11p and 13q in primary hepatocellular carcinomas. Cytogenet Cell Genet 48:72–78. https://doi.org/10.1159/000132593 CrossRefPubMed

Wang H et al (2018) Long noncoding RNA miR503HG, a prognostic indicator, inhibits tumor metastasis by regulating the HNRNPA2B1/NF-kappaB pathway in hepatocellular carcinoma. Theranostics 8:2814–2829. https://doi.org/10.7150/thno.23012 CrossRefPubMedPubMedCentral

Xie C et al (2011) KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res 39:W316–W322. https://doi.org/10.1093/nar/gkr483 CrossRefPubMedPubMedCentral

Yao J et al (2017) Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma. Mol Cancer 16:164. https://doi.org/10.1186/s12943-017-0733-5 CrossRefPubMedPubMedCentral

Yuan SX et al (2012) Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology 56:2231–2241. https://doi.org/10.1002/hep.25895 CrossRefPubMed

Zhou XD (2002) Recurrence and metastasis of hepatocellular carcinoma: progress and prospects. Hepatobil Pancreat Dis Int 1:35–41

Titel: A liver-specific lncRNA, FAM99B, suppresses hepatocellular carcinoma progression through inhibition of cell proliferation, migration, and invasion
verfasst von: Meile Mo
Shun Liu
Xiaoyun Ma
Chao Tan
Liangjia Wei
Yonghong Sheng
Yanye Song
Xiaoyun Zeng
Dongping Huang
Xiaoqiang Qiu
Publikationsdatum: 26.06.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02954-8

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A liver-specific lncRNA, FAM99B, suppresses hepatocellular carcinoma progression through inhibition of cell proliferation, migration, and invasion

Abstract

Background

Methods

Results

Conclusion

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

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