Tumor Biology

, Volume 36, Issue 4, pp 2947–2955 | Cite as

Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma

  • Hai-min Zhang
  • Feng-qiang Yang
  • Shao-Jun Chen
  • Jianping Che
  • Jun-hua Zheng
Research Article

Abstract

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.

Keywords

MALAT1 Clear cell renal cell carcinoma Proliferation Invasion Migration 

Notes

Conflicts of interest

None.

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Yang FQ, Yang FP, Li W, et al. Foxl1 inhibits tumor invasion and predicts outcome in human renal cancer. Int J Clin Exp Pathol. 2014;7(1):110.PubMedGoogle Scholar
  3. 3.
    Russo P. Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol. 2000;27(2):160–76.PubMedGoogle Scholar
  4. 4.
    Motzer RJ, Molina AM. Targeting renal cell carcinoma. J Clin Oncol. 2009;27(20):3274–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discov. 2011;1(5):391–407.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74.CrossRefPubMedGoogle Scholar
  7. 7.
    Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wang P, Ren Z, Sun P. Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem. 2012;113:1868–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Han Y, Liu Y, Gui Y, et al. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol. 2013;107(5):555–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Xie H W, Wu Q Q, Zhu B, et al. Long noncoding RNA SPRY4-IT1 is upregulated in esophageal squamous cell carcinoma and associated with poor prognosis. Tumor Biology. 2014;1–12.Google Scholar
  12. 12.
    Tripathi V, Ellis JD, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010;39(6):925–38.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22(39):8031–41.CrossRefPubMedGoogle Scholar
  14. 14.
    Lai M, Yang Z, Zhou L, et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol. 2012;29(3):1810–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Liu JH, Chen G, Dang YW, et al. Expression and prognostic significance of lncRNA MALAT1 in pancreatic cancer tissues. Asian Pac J Cancer Prev. 2014;15(7):2971.CrossRefPubMedGoogle Scholar
  16. 16.
    Gutschner T, Hämmerle M, Eißmann M, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73(3):1180–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Yang L, Lin C, Liu W, et al. ncRNA-and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell. 2011;147(4):773–88.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wu XS, Wang XA, Wu WG, et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther. 2014;15(6):0–1.Google Scholar
  19. 19.
    Tee AE, Ling D, Nelson C, et al. The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. Oncotarget. 2014;5(7):1793–804.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Carninci P, Kasukawa T, Katayama S, et al. The transcriptional landscape of the mammalian genome. Science. 2005;309(5740):1559–63.CrossRefPubMedGoogle Scholar
  21. 21.
    Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74.CrossRefPubMedGoogle Scholar
  22. 22.
    Gutschner T, Hämmerle M, Diederichs S. MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med. 2013;91(7):791–801.CrossRefPubMedGoogle Scholar
  23. 23.
    Guo F, Li Y, Liu Y, et al. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin. 2010;42(3):224–9.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Hai-min Zhang
    • 1
  • Feng-qiang Yang
    • 1
  • Shao-Jun Chen
    • 1
  • Jianping Che
    • 1
  • Jun-hua Zheng
    • 1
  1. 1.Department of Urology, Shanghai Tenth People’s HospitalTongji UniversityShanghaiChina

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