Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

Small nucleolar RNA 113–1 suppresses tumorigenesis in hepatocellular carcinoma

Authors: Gang Xu, Fang Yang, Cui-Ling Ding, Lan-Juan Zhao, Hao Ren, Ping Zhao, Wen Wang, Zhong-Tian Qi

Published in: Molecular Cancer | Issue 1/2014

Login to get access

Abstract

Background

Emerging evidence suggests that small nucleolar RNAs (snoRNAs) are involved in tumorigenesis. The roles of small nucleolar RNA 113–1 (SNORD113-1) on the development of hepatocellular carcinoma (HCC) remain unknown.

Methods

The expression of SNORD113-1 was measured in 112 HCC tumor tissues using quantitative RT-PCR and compared with expression levels from with paired non-tumor tissues. The effects of SNORD113-1 on HCC tumorigenesis were investigated in HepG2 and Huh7 cells as well as a xenograft nude mouse model. CpG methylation within the promoter region of the SNORD113-1 gene was identified using Sodium bisulfite sequencing. Cancer pathway reporter investigate the mechanism by which SNORD113-1 suppressed tumorigenesis.

Results

SNORD113-1 expression was significantly downregulated in HCC tumors compared with adjacent non-tumor tissues, and downregulation of SNORD113-1 in HCC tumors was significantly associated with worse survival of patients. In addition, CpG methylation at the promoter region of the SNORD113-1 gene was higher in HCC tumors than adjacent non-tumor tissues. Functionally, SNORD113-1 suppressed cancer cell growth in HepG2 and Huh7 cells and in a xenograft nude mouse model. Furthermore, SNORD113-1 inactivated the phosphorylation of ERK1/2 and SMAD2/3 in MAPK/ERK and TGF-β pathways.

Conclusions

SNORD113-1 functions as a tumor suppressor role in HCC and may be important as a potential diagnostic and therapeutic target for HCC.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107CrossRefPubMed
2.
Aravalli RN, Steer CJ, Cressman EN: Molecular mechanisms of hepatocellular carcinoma. Hepatology. 2008, 48: 2047-2063. 10.1002/hep.22580CrossRefPubMed
3.
4.
Shi X, Sun M, Liu H, Yao Y, Song Y: Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett. 2013, 339: 159-166. 10.1016/j.canlet.2013.06.013CrossRefPubMed
5.
Mannoor K, Liao J, Jiang F: Small nucleolar RNAs in cancer. Biochim Biophys Acta. 1826, 2012: 121-128.
6.
Matera AG, Terns RM, Terns MP: Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 2007, 8: 209-220. 10.1038/nrm2124CrossRefPubMed
7.
Mei YP, Liao JP, Shen J, Yu L, Liu BL, Liu L, Li RY, Ji L, Dorsey SG, Jiang ZR, Katz RL, Wang JY, Jiang F: Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene. 2012, 31: 2794-2804. 10.1038/onc.2011.449CrossRefPubMed
8.
Liao J, Yu L, Mei Y, Guarnera M, Shen J, Li R, Liu Z, Jiang F: Small nucleolar RNA signatures as biomarkers for non-small-cell lung cancer. Mol Cancer. 2010, 9: 198- 10.1186/1476-4598-9-198PubMedCentralCrossRefPubMed
9.
Valleron W, Ysebaert L, Berquet L, Fataccioli V, Quelen C, Martin A, Parrens M, Lamant L, de Leval L, Gisselbrecht C, Gaulard P, Brousset P: Small nucleolar RNA expression profiling identifies potential prognostic markers in peripheral T-cell lymphoma. Blood. 2012, 120: 3997-4005. 10.1182/blood-2012-06-438135CrossRefPubMed
10.
Benetatos L, Hatzimichael E, Londin E, Vartholomatos G, Loher P, Rigoutsos I, Briasoulis E: The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis. Cell Mol Life Sci. 2013, 70: 795-814. 10.1007/s00018-012-1080-8CrossRefPubMed
11.
Song P, Gao J, Inagaki Y, Kokudo N, Hasegawa K, Sugawara Y, Tang W: Biomarkers: evaluation of screening for and early diagnosis of hepatocellular carcinoma in Japan and China. Liver Cancer. 2013, 2: 31-39. 10.1159/000346220PubMedCentralCrossRefPubMed
12.
Filmus J, Capurro M: Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma. FEBS J. 2013, 280: 2471-2476. 10.1111/febs.12126CrossRefPubMed
13.
Miyasaka Y, Enomoto N, Nagayama K, Izumi N, Marumo F, Watanabe M, Sato C: Analysis of differentially expressed genes in human hepatocellular carcinoma using suppression subtractive hybridization. Br J Cancer. 2001, 85: 228-234. 10.1054/bjoc.2001.1901PubMedCentralCrossRefPubMed
14.
Heringlake S, Hofdmann M, Fiebeler A, Manns MP, Schmiegel W, Tannapfel A: Identification and expression analysis of the aldo-ketoreductase1-B10 gene in primary malignant liver tumours. J Hepatol. 2010, 52: 220-227. 10.1016/j.jhep.2009.11.005CrossRefPubMed
15.
Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, Sangrajrang S, Hainaut P, Marrero JA, Beretta L: Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology. 2012, 55: 483-490. 10.1002/hep.24703PubMedCentralCrossRefPubMed
16.
Muir K, Hazim A, He Y, Peyressatre M, Kim DY, Song X, Beretta L: Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma. Cancer Res. 2013, 73: 4722-4731. 10.1158/0008-5472.CAN-12-3797CrossRefPubMed
17.
Marshall A, Lukk M, Kutter C, Davies S, Alexander G, Odom DT: Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker. PLoS One. 2013, 8: e59459- 10.1371/journal.pone.0059459PubMedCentralCrossRefPubMed
18.
Fu L, Dong SS, Xie YW, Tai LS, Chen L, Kong KL, Man K, Xie D, Li Y, Cheng Y, Tao Q, Guan XY: Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma. Hepatology. 2010, 51: 1624-1634. 10.1002/hep.23540CrossRefPubMed
19.
Bitton-Worms K, Pikarsky E, Aronheim A: The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice. Mol Cancer. 2010, 9: 54- 10.1186/1476-4598-9-54PubMedCentralCrossRefPubMed
20.
Tsunedomi R, Iizuka N, Hamamoto Y, Uchimura S, Miyamoto T, Tamesa T, Okada T, Takemoto N, Takashima M, Sakamoto K, Hamada K, Yamada-Okabe H, Oka M: Patterns of expression of cytochrome P450 genes in progression of hepatitis C virus-associated hepatocellular carcinoma. Int J Oncol. 2005, 27: 661-667.PubMed
21.
Wang B, Hsu SH, Frankel W, Ghoshal K, Jacob ST: Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. Hepatology. 2012, 56: 186-197. 10.1002/hep.25632PubMedCentralCrossRefPubMed
22.
Dong XY, Guo P, Boyd J, Sun X, Li Q, Zhou W, Dong JT: Implication of snoRNA U50 in human breast cancer. J Genet Genomics. 2009, 36: 447-454. 10.1016/S1673-8527(08)60134-4PubMedCentralCrossRefPubMed
23.
Dong XY, Rodriguez C, Guo P, Sun X, Talbot JT, Zhou W, Petros J, Li Q, Vessella RL, Kibel AS, Stevens VL, Calle EE, Dong JT: SnoRNA U50 is a candidate tumorsuppressor gene at 6q14.3 with a mutation associated with clinically significant prostate cancer. Hum Mol Genet. 2008, 17: 1031-1042.PubMedCentralCrossRefPubMed
24.
Horsthemke B, Wagstaff J: Mechanisms of imprinting of the Prader-Willi/Angelman region. Am J Med Genet A. 2008, 146: 2041-2052.CrossRef
25.
Piao Z, Park C, Park JH, Kim H: Allelotype analysis of hepatocellular carcinoma. Int J Cancer. 1998, 75: 29-33. 10.1002/(SICI)1097-0215(19980105)75:1<29::AID-IJC5>3.0.CO;2-3CrossRefPubMed
26.
Bando T, Kato Y, Ihara Y, Yamagishi F, Tsukada K, Isobe M: Loss of heterozygosity of 14q32 in colorectal carcinoma. Cancer Genet Cytogenet. 1999, 111: 161-165. 10.1016/S0165-4608(98)00242-8CrossRefPubMed
27.
Croce CM: Genetic approaches to the study of the molecular basis of human cancer. Cancer Res. 1991, 51: 5015s-5018s.PubMed
28.
Zhang X, Zhou YL, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A: A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab. 2003, 88: 5119-5126. 10.1210/jc.2003-030222CrossRefPubMed
29.
Kiss T: Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell. 2002, 109: 145-148. 10.1016/S0092-8674(02)00718-3CrossRefPubMed
30.
Tycowski KT, Aab A, Steitz JA: Guide RNAs with 5′ caps and novel box C/D snoRNA-like domains formodification of snRNAs inmetazoa. Curr Biol. 2004, 4: 1985-1995.CrossRef
31.
Chien CH, Sun YM, Chang WC, Chiang-Hsieh PY, Lee TY, Horng JT, Tsou AP, Huang HD: Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data. Nucleic Acids Res. 2011, 39: 9345-9356. 10.1093/nar/gkr604PubMedCentralCrossRefPubMed
32.
Suzuki Y, Ishihara D, Sasaki M, Nakagawa H, Hata H, Tsunoda T, Watanabe M, Komatsu T, Ota T, Isogai T, Suyama A, Sugano S: Statistical analysis of the 5′ untranslated region of human mRNA using “Oligo-Capped” cDNA libraries. Genomics. 2000, 64: 286-297. 10.1006/geno.2000.6076CrossRefPubMed
33.
Ferreira HJ, Heyn H, Moutinho C, Esteller M: CpG island hypermethylation-associated silencing of small nucleolar RNAs in human cancer. RNA Biol. 2012, 9: 881-890. 10.4161/rna.19353PubMedCentralCrossRefPubMed
34.
Zhang X, Gejman R, Mahta A, Zhong Y, Rice KA, Zhou Y, Cheunsuchon P, Louis DN, Klibanski A: Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Res. 2010, 70: 2350-2358. 10.1158/0008-5472.CAN-09-3885PubMedCentralCrossRefPubMed
35.
Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A: Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab. 2005, 90: 2179-2186. 10.1210/jc.2004-1848CrossRefPubMed
36.
Benetatos L, Dasoula A, Hatzimichael E, Georgiou I, Syrrou M, Bourantas KL: Promoter hypermethylation of the MEG3 (DLK1/MEG3) imprinted gene inmultiple myeloma. Clin Lymphoma Myeloma. 2008, 8: 171-175. 10.3816/CLM.2008.n.021CrossRefPubMed
37.
Ozsolak F, Poling LL, Wang Z, Liu H, Liu XS, Roeder RG, Zhang X, Song JS, Fisher DE: Chromatin structure analyses identify miRNA promoters. Genes Dev. 2008, 22: 3172-3183. 10.1101/gad.1706508PubMedCentralCrossRefPubMed
38.
Barski A, Jothi R, Cuddapah S, Cui K, Roh TY, Schones DE, Zhao K: Chromatin poises miRNA-and protein-coding genes for expression. Genome Res. 2009, 19: 1742-1751. 10.1101/gr.090951.109PubMedCentralCrossRefPubMed
39.
Bajic VB, Tan SL, Suzuki Y, Sugano S: Promoter prediction analysis on the whole human genome. Nat Biotechnol. 2004, 22: 1467-1473. 10.1038/nbt1032CrossRefPubMed
40.
Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaillé J: A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res. 2004, 14: 1741-1748. 10.1101/gr.2743304PubMedCentralCrossRefPubMed
41.
Manodoro F, Marzec J, Chaplin T, Miraki-Moud F, Moravcsik E, Jovanovic JV: Loss of imprinting at the 14q32 domain is associated with microRNA overexpression in acute promyelocytic leukemia. Blood. 2014, 123: 2066-2074. 10.1182/blood-2012-12-469833CrossRefPubMed
42.
Ni J, Tien AL, Fournier MJ: Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell. 1997, 89: 565-573. 10.1016/S0092-8674(00)80238-XCrossRefPubMed
43.
44.
Yin QF, Yang L, Zhang Y, Xiang JF, Wu YW, Carmichael GG, Chen LL: Long noncoding RNAs with snoRNA ends. Mol Cell. 2012, 48: 219-230. 10.1016/j.molcel.2012.07.033CrossRefPubMed
45.
Kondoh NI, Wakatsuki T, Hada A, Shuda M, Tanaka K, Arai M, Yamamoto M: Genetic and epigenetic events in human hepatocarcinogenesis. Int J Oncol. 2001, 18 (6): 1271-1278.PubMed
46.
47.
Huynh H, Nguyen TT, Chow KH, Tan PH, Soo KC, Tran E: Over-expression of the mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK in hepatocellular carcinoma: its role in tumor progression and apoptosis. BMC Gastroenterol. 2003, 3: 19- 10.1186/1471-230X-3-19PubMedCentralCrossRefPubMed
48.
Calvisi DF, Pascale RM, Feo F: Dissection of signal transduction pathways as a tool for the development of targeted therapies of hepatocellular carcinoma. Rev Recent Clin Trials. 2007, 2: 217-236. 10.2174/157488707781662715CrossRefPubMed
Metadata
Title
Small nucleolar RNA 113–1 suppresses tumorigenesis in hepatocellular carcinoma
Authors
Gang Xu
Fang Yang
Cui-Ling Ding
Lan-Juan Zhao
Hao Ren
Ping Zhao
Wen Wang
Zhong-Tian Qi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-216

Other articles of this Issue 1/2014

Molecular Cancer 1/2014 Go to the issue

Research

Inhibition of the checkpoint kinase Chk1 induces DNA damage and cell death in human Leukemia and Lymphoma cells

Research

miR-300 inhibits epithelial to mesenchymal transition and metastasis by targeting Twist in human epithelial cancer

Research

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

Research

Supraphysiological androgen levels induce cellular senescence in human prostate cancer cells through the Src-Akt pathway

Research

Clinical relevance and therapeutic potential of angiopoietin-like protein 4 in hepatocellular carcinoma

Research

cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits