Skip to main content
Erschienen in: Medical Oncology 3/2012

01.09.2012 | Original Paper

Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation

verfasst von: Ming-chun Lai, Zhe Yang, Lin Zhou, Qian-qian Zhu, Hai-yang Xie, Feng Zhang, Li-ming Wu, Lei-ming Chen, Shu-sen Zheng

Erschienen in: Medical Oncology | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. In the present study, we evaluated the expression of MALAT1 by quantitative real-time PCR in 9 liver cancer cell lines and 112 HCC cases including 60 cases who received liver transplantation (LT) with complete follow-up data. Moreover, small interfering RNA (siRNA) was used to inhibit MALAT1 expression to investigate its biological role in tumor progression. We found that MALAT1 was up-regulated in both cell lines and clinical tissue samples. Patients with high expression level of MALAT1 had a significantly increased risk of tumor recurrence after LT, particularly in patients who exceeded the Milan criteria. On multivariate analysis, MALAT1 was an independent prognostic factor for predicting HCC recurrence (hazard ratio, 3.280, P = 0.003).In addition, inhibition of MALAT1 in HepG2 cells could effectively reduce cell viability, motility, invasiveness, and increase the sensitivity to apoptosis. Our data suggest that lncRNA MALAT1 play an important role in tumor progression and could be a novel biomarker for predicting tumor recurrence after LT and serve as a promising therapeutic target.
Literatur
1.
Zurück zum Zitat Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, Ijiri K, Akimitsu N. MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 2010;584:4575–80.PubMedCrossRef Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, Ijiri K, Akimitsu N. MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 2010;584:4575–80.PubMedCrossRef
3.
Zurück zum Zitat Belghiti J, Kianmanesh R. Surgical treatment of hepatocellular carcinoma. HPB (Oxford). 2005;7:42–9.CrossRef Belghiti J, Kianmanesh R. Surgical treatment of hepatocellular carcinoma. HPB (Oxford). 2005;7:42–9.CrossRef
4.
Zurück zum Zitat Bai DS, Dai Z, Zhou J, et al. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology. 2009;49:460–70.PubMedCrossRef Bai DS, Dai Z, Zhou J, et al. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology. 2009;49:460–70.PubMedCrossRef
5.
Zurück zum Zitat Sieghart W, Wang X, Schmid K, et al. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol. 2011;54:89–97.PubMedCrossRef Sieghart W, Wang X, Schmid K, et al. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol. 2011;54:89–97.PubMedCrossRef
6.
Zurück zum Zitat Yang Y, Nagano H, Ota H, et al. Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery. 2007;141:196–202.PubMedCrossRef Yang Y, Nagano H, Ota H, et al. Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery. 2007;141:196–202.PubMedCrossRef
7.
Zurück zum Zitat Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85:1726–32.PubMedCrossRef Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85:1726–32.PubMedCrossRef
8.
Zurück zum Zitat Ørom UA, Derrien T, Beringer M, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143:46–58.PubMedCrossRef Ørom UA, Derrien T, Beringer M, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143:46–58.PubMedCrossRef
9.
Zurück zum Zitat Chen LL, Gordon G. Long noncoding RNAs in mammalian cells: what, where, and why. WIREs RNA. 2010;1:2–21.PubMed Chen LL, Gordon G. Long noncoding RNAs in mammalian cells: what, where, and why. WIREs RNA. 2010;1:2–21.PubMed
10.
Zurück zum Zitat Guo F, Li Y, Liu Y, Wang J, Li Y, Li G. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin (Shanghai). 2010;42:224–9.CrossRef Guo F, Li Y, Liu Y, Wang J, Li Y, Li G. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin (Shanghai). 2010;42:224–9.CrossRef
11.
Zurück zum Zitat Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.PubMedCrossRef Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.PubMedCrossRef
12.
Zurück zum Zitat Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031–41.PubMedCrossRef Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031–41.PubMedCrossRef
13.
Zurück zum Zitat Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26:851–8.PubMedCrossRef Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26:851–8.PubMedCrossRef
14.
Zurück zum Zitat Luo JH, Ren B, Keryanov S, et al. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology. 2006;44:1012–24.PubMedCrossRef Luo JH, Ren B, Keryanov S, et al. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology. 2006;44:1012–24.PubMedCrossRef
15.
Zurück zum Zitat Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, Noguchi M. Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci. 2006;97:106–12.PubMedCrossRef Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, Noguchi M. Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci. 2006;97:106–12.PubMedCrossRef
16.
Zurück zum Zitat Bioulac-Sage P, Rebouissou S, Sa Cunha A, et al. Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology. 2005;128:1211–8.PubMedCrossRef Bioulac-Sage P, Rebouissou S, Sa Cunha A, et al. Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology. 2005;128:1211–8.PubMedCrossRef
17.
Zurück zum Zitat Feng YX, Zhao JS, Li JJ, et al. Liver cancer EphrinA2 promotes tumorigenicity through Rac1 Akt NF-kappaB signaling pathway 120. Hepatology. 2010;51:535–44.PubMedCrossRef Feng YX, Zhao JS, Li JJ, et al. Liver cancer EphrinA2 promotes tumorigenicity through Rac1 Akt NF-kappaB signaling pathway 120. Hepatology. 2010;51:535–44.PubMedCrossRef
18.
Zurück zum Zitat Huang G, Hu Z, Li M, Cui Y, Li Y, Guo L, Jiang W, Lu SH. ECRG2 inhibits cancer cell migration, invasion and metastasis through the downregulation of uPA/plasmin activity. Carcinogenesis. 2007;28:2274–81.PubMedCrossRef Huang G, Hu Z, Li M, Cui Y, Li Y, Guo L, Jiang W, Lu SH. ECRG2 inhibits cancer cell migration, invasion and metastasis through the downregulation of uPA/plasmin activity. Carcinogenesis. 2007;28:2274–81.PubMedCrossRef
19.
Zurück zum Zitat Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.PubMedCrossRef Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.PubMedCrossRef
20.
Zurück zum Zitat Song HY, Liu YK, Feng JT, et al. Proteomic analysis on metastasis-associated proteins of human hepatocellular carcinoma tissues. J Cancer Res Clin Oncol. 2006;132:92–8.PubMedCrossRef Song HY, Liu YK, Feng JT, et al. Proteomic analysis on metastasis-associated proteins of human hepatocellular carcinoma tissues. J Cancer Res Clin Oncol. 2006;132:92–8.PubMedCrossRef
21.
Zurück zum Zitat Grasso A, Stigliano R, Morisco F, et al. Liver transplantation and recurrent hepatocellular carcinoma: predictive value of nodule size in a retrospective and explant study. Transplantation. 2006;81:1532–41.PubMedCrossRef Grasso A, Stigliano R, Morisco F, et al. Liver transplantation and recurrent hepatocellular carcinoma: predictive value of nodule size in a retrospective and explant study. Transplantation. 2006;81:1532–41.PubMedCrossRef
22.
Zurück zum Zitat Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.PubMedCrossRef Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.PubMedCrossRef
23.
Zurück zum Zitat Calin GA, Liu CG, Ferracin M, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12:215–29.PubMedCrossRef Calin GA, Liu CG, Ferracin M, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12:215–29.PubMedCrossRef
24.
Zurück zum Zitat Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;7:3–7.CrossRef Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;7:3–7.CrossRef
25.
Zurück zum Zitat Tseng JJ, Hsieh YT, Hsu SL, Chou MM. Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro. Mol Hum Reprod. 2009;15:725–31.PubMedCrossRef Tseng JJ, Hsieh YT, Hsu SL, Chou MM. Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro. Mol Hum Reprod. 2009;15:725–31.PubMedCrossRef
Metadaten
Titel
Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation
verfasst von
Ming-chun Lai
Zhe Yang
Lin Zhou
Qian-qian Zhu
Hai-yang Xie
Feng Zhang
Li-ming Wu
Lei-ming Chen
Shu-sen Zheng
Publikationsdatum
01.09.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 3/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-0004-z

Weitere Artikel der Ausgabe 3/2012

Medical Oncology 3/2012 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.