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http://dx.doi.org/10.7314/APJCP.2014.15.23.10513

Long Non-coding RNAs are Differentially Expressed in Hepatocellular Carcinoma Cell Lines with Differing Metastatic Potential  

Fang, Ting-Ting (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Sun, Xiao-Jing (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Chen, Jie (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Zhao, Yan (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Sun, Rui-Xia (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Ren, Ning (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Liu, Bin-Bin (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.23, 2015 , pp. 10513-10524 More about this Journal
Abstract
Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.
Keywords
Hepatocellular carcinoma; organ-specific metastasis; long non-coding RNA; RP5-1014O16.1; expression;
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1 de Kok JB, Verhaegh GW, Roelofs RW, et al (2002). DD3 (PCA3)., a very sensitive and specific marker to detect prostate tumors. Cancer Res, 62, 2695-8.
2 Dexter DL, Kowalski HM, Blazar BA, et al (1978). Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res, 38, 3174-81.
3 Fejes-Toth K, Sotirova V, Sachidanandam R, et al (2009). Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs. Nature, 457, 1028-32.   DOI   ScienceOn
4 Fritah A, Saucier C, De Wever O, et al (2008). Role of WISP-2/ CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells. Mol Cell Biol, 28, 1114-23.   DOI
5 Genda T, Ichida T, Kojiro M, et al (1999). Cell motility mediated by Rho and Rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma. Hepatology, 30, 1027-36.   DOI
6 Gesierich S, Berezovskiy I, Ryschich E, et al (2006). Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res, 66, 7083-94.   DOI
7 Guo FJ, Li YL, Liu Y, et al (2010). Inhibition of metastasisassociated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin, 42, 224-9.   DOI   ScienceOn
8 Gupta RA, Shah N, Wang KC, et al (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 464, 1071-6.   DOI   ScienceOn
9 Guttman M, Amit I, Garber M, et al (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458, 223-7.   DOI
10 Kapranov P, Cawley SE, Drenkow J, et al (2002). Large-scale transcriptional activity in chromosomes 21 and 22. Science, 296, 916-9.   DOI
11 Khalil AM, Guttman M, Huarte M, et al (2009). Many human large intergenic noncoding RNAs associate with chromatinmodifying complexes and affect gene expression. Proc Natl Acad Sci U S A, 106, 11667-72.   DOI
12 Kmita M, Duboule D (2003). Organizing axes in time and space; 25 years of colinear tinkering. Science, 301, 331-3.   DOI
13 Lemons D, McGinnis W (2006). Genomic evolution of Hox gene clusters. Science, 313, 1918-22.   DOI
14 Li Y, Tang Y, Ye L, et al (2003). Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol, 129, 43-51.
15 Li Y, Tang ZY, Ye SL, et al (2001). Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol, 7, 630-6.
16 Lin R, Maeda S, Liu C, et al (2007). A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene, 26, 851-8.   DOI
17 Llovet JM, Lencioni R, Gaile PR, et al (2012). EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 56, 908-43.   DOI   ScienceOn
18 Lu X, Kang Y (2007). Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia, 12, 153-62.   DOI
19 Matouk IJ, Abbasi I, Hochberg A, et al (2009). Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis. Eur J Gastroenterol Hepatol, 21, 688-92.   DOI
20 Seto M, Ohta M, Ikenoue T, et al (2011). Reduced expression of RAS protein activator like-1 in gastric cancer. Int J Cancer, 128, 1293-302.   DOI   ScienceOn
21 Simon JA, Kingston RE (2009). Mechanisms of Polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol, 10, 697-708.   DOI
22 Smedley D, Sidhar S, Birdsall S, et al (2000). Characterization of chromosome 1 abnormalities in malignant melanomas. Genes Chromosomes Cancer, 28, 121-5.   DOI
23 Sporn JC, Kustatscher G, Hothorn T, et al (2009). Histone macroH2A isoforms predict the risk of lung cancer recurrence. Oncogene, 28, 3423-8.   DOI
24 Subramanian A, Tamayo P, Mootha VK, et al (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA, 102, 15545-50.   DOI
25 Sun FX, Tang ZY, Lui KD, et al (1996). Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer, 66, 239-43.   DOI
26 Taft RJ, Pang KC, Mercer TR, et al (2010). Non-coding RNAs: regulators of disease. J Pathol, 220, 126-39.   DOI   ScienceOn
27 Talmadge JE, Fidler IJ (2010). AACR Centrspective. Cancer Res, 70, 5649-69.   DOI
28 Tinzl M, Horvath S (2004). DD3 (PCA3). RNA analysis in urine - A new perspective for detecting prostate cancer. Eur Urol, 46, 182-7.   DOI
29 Uchino H, Kataoka H, Itoh H, et al (2000). Overexpression of intestinal trefoil factor in human colon carcinoma cells reduces cellular growth in vitro and in vivo. Gastroenterol, 118, 60-9.   DOI
30 Barabasi AL (2004). Network biology: Understanding the cell's functional organization. Nat Rev Genet, 5, 101-15.   DOI
31 Bartel DP (2009). MicroRNAs: Target Recognition and Regulatory Functions. Cell, 136, 215-33.   DOI
32 Berteaux N, Aptel N, Cathala G, et al (2008). A novel H19 antisense rna overexpressed in breast cancer contributes to paternal IGF2 expression. Mol Cell Biol, 28, 6731-45.   DOI
33 Bertone P, Stolc V, Royce TE, et al (2004). Global identification of human transcribed sequences with genome tiling arrays. Science, 306, 2242-6.   DOI   ScienceOn
34 Braconi C, Valeri N, Kogure T, et al (2011). Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma. Proc Nat Acad Sci USA, 108, 786-91.   DOI   ScienceOn
35 Bussemakers M, Verhaegh GW, Karthaus H, et al (1999). DD3: A new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res, 59.
36 Cabili MN, Trapnell C, Goff L, et al (2011). Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev, 25, 1915-27.   DOI   ScienceOn
37 Chen W, Bocker W, Brosius J, et al (1997). Expression of neural BC200 RNA in human tumours. J Pathol, 183, 345-51.   DOI
38 Da Sacco L, Baldassarre A, Masotti A (2012). Bioinformatics Tools and Novel Challenges in Long Non-Coding RNAs (lncRNAs). Functional Analysis. Int J Mol Sci, 13, 97-114.
39 Guttman M, Rinn JL (2012). Modular regulatory principles of large non-coding RNAs. Nature, 482, 339-46.   DOI   ScienceOn
40 Guttman M, Donaghey J, Carey BW, et al (2011). lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature, 477, 295-300.   DOI
41 Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.   DOI
42 He Y, Meng XM, Huang C, et al (2014). Long noncoding RNAs: Novel insights into hepatocelluar carcinoma. Cancer Lett, 344, 20-7.   DOI
43 Hibi K, Nakamura H, Hirai A, et al (1996). Loss of H19 imprinting in esophageal cancer. Cancer Res, 56, 480-2.
44 Hong SS, Kim TK, Sung KB, et al (2003). Extrahepatic spread of hepatocellular carcinoma: a pictorial review. Eur Radiol, 13, 874-82.
45 Iacoangeli A, Lin Y, Morley EJ, et al (2004). BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis, 25, 2125-33.   DOI
46 Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA-Cancer J Clin, 61, 69-90.   DOI
47 Ji P, Wang WB, Metzger R, et al (2003). MALAT-1, a novel noncoding RNA, and thymosin beta 4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 22, 8031-41.   DOI
48 Kanetaka K, Sakamoto M, Yamamoto Y, et al (2001). Overexpression of tetraspanin CO-029 in hepatocellular carcinoma. J Hepatol, 35, 637-42.   DOI
49 Kanetaka K, Sakamoto M, Yamamoto Y, et al (2003). Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells. J Gastroenterol Hepatol, 18, 1309-14.   DOI
50 Mercer TR, Dinger ME, Mattick JS (2009). Long non-coding RNAs: insights into functions. Nat Rev Genet, 10, 155-9.   DOI   ScienceOn
51 Mootha VK, Lindgren CM, Eriksson KF, et al (2003). PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet, 34, 267-73.   DOI
52 Mourtada-Maarabouni M, Pickard MR, Hedge VL, et al (2009). GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene, 28, 195-208.   DOI   ScienceOn
53 Nguyen DX, Bos PD, Massague J (2009). Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer, 9, 274-84.   DOI
54 Nupponen NN, Carpten JD (2001). Prostate cancer susceptibility genes: many studies, many results, no answers. Cancer Metastasis Rev, 20, 155-64.   DOI
55 Ohta M, Seto M, Miyabayashi K, et al (2009). Decreased expression of the RAS-GTPase activating protein RASAL1 is associated with colorectal tumor progression. Gastroenterology, 136, 206-16.   DOI   ScienceOn
56 Okazaki Y, Furuno M, Kasukawa T, et al (2002). Analysis of the mouse transcriptome based on functional annotation of 60, 770 full-length cDNAs. Nature, 420, 563-73.   DOI   ScienceOn
57 Orom UA, Derrien T, Beringer M, et al (2010). Long Noncoding RNAs with Enhancer-like Function in Human Cells. Cell, 143, 46-58.   DOI
58 Panzitt K, Tschernatsch MM, Guelly C, et al (2007). Characterization of HULC, a novel gene with striking upregulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology, 132, 330-42.   DOI   ScienceOn
59 Wang Y, Liu XJ, Yao XD (2014). Function of PCA3 in prostate tissue and clinical research progress on developing a PCA3 score. Chin J Cancer Res, 26, 493-500.
60 Wang JY, Liu XF, Wu HC, et al (2010). CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res, 38, 5366-83.   DOI
61 Wapinski O, Chang HY (2011). Long noncoding RNAs and human disease. Trends Cell Biol, 21, 354-61.   DOI   ScienceOn
62 Wilusz JE, Sunwoo H, Spector DL (2009). Long noncoding RNAs: functional surprises from the RNA world. Genes Dev, 23, 1494-504.   DOI
63 Xie H, Ma H, Zhou D (2013). Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. Biomed Res Int, 2013, 136106.
64 Yamada K, Kano J, Tsunoda H, et al (2006). Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci, 97, 106-12.   DOI
65 Yang F, Zhang L, Huo XS, et al (2011). Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology, 54, 1679-89.   DOI   ScienceOn
66 Ye QH, Forgues M, Kim JW, et al (2003). Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med, 9, 416-23.   DOI
67 Yue S, Mu W, Zoller M (2013). Tspan8 and CD151 promote metastasis by distinct mechanisms. Eur J Cancer, 49, 2934-48.   DOI
68 Zhang EB, Han L, Yin DD, et al (2014). c-Myc-induced, long, noncoding H19 affects cell proliferation and predicts a poor prognosis in patients with gastric cancer. Med Oncol, 31, 914.   DOI
69 Ponting CP, Oliver PL, Reik W (2009). Evolution and Functions of Long Noncoding RNAs. Cell, 136, 629-41.   DOI
70 Pibouin L, Villaudy J, Ferbus D, et al (2002). Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas. Cancer Genet Cytogenet, 133, 55-60.   DOI
71 Poon R, Wong J (2000). Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg, 232.
72 Prieto C, Risueno A, Fontanillo C, et al (2008). Human gene coexpression landscape: confident network derived from tissue transcriptomic profiles. PLoS Onee, 3.
73 Qiao HP, Gao WS, Huo JX, et al (2013). Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev, 14, 1077-82.   과학기술학회마을   DOI   ScienceOn
74 Qiu MT, Hu JW, Yin R, et al (2013). Long noncoding RNA: an emerging paradigm of cancer research. Tumour Biol, 34, 613-20.   DOI
75 Rangel L, Wernyj RP, Cho KR (2003). Characterization of novel human ovarian cancer-specific transcripts (HOSTs). identified by serial analysis of gene expression. Oncogene, 22, 7225-32.   DOI
76 Ren S, Wang F, Shen J, et al (2013). Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer, 49, 2949-59.   DOI
77 Rinn JL, Wang JK, Xu X, et al (2007). Functional demarcation of active and silent chromatin domains in human HOX loci by Noncoding RNAs. Cell, 129, 1311-23.   DOI
78 Zhang H, Cai K, Wang J, et al (2014). MiR-7, Inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway. Stem Cells, 32, 2858-68.   DOI