Asian Pacific Journal of Cancer Prevention

Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Expression and Prognostic Significance of lncRNA MALAT1 in Pancreatic Cancer Tissues

  • Liu, Jiang-Hua (Department of Emergency, First Affiliated Hospital of Guangxi Medical University) ;
  • Chen, Gang (Department of Pathology, First Affiliated Hospital of Guangxi Medical University) ;
  • Dang, Yi-Wu (Department of Pathology, First Affiliated Hospital of Guangxi Medical University) ;
  • Li, Chun-Jun (Department of Pathology, First Affiliated Hospital of Guangxi Medical University) ;
  • Luo, Dian-Zhong (Department of Pathology, First Affiliated Hospital of Guangxi Medical University)
  • Published : 2014.04.01

Abstract

Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

Keywords

Pancreatic cancer;long non-coding RNA;MALAT1;survival;prognosis

File

Download PDF

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Weber DG, Johnen G, Casjens S, et al (2013). Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes, 6, 518. https://doi.org/10.1186/1756-0500-6-518
  2. Tian D, Sun S, Lee JT (2010). The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143, 390-403. https://doi.org/10.1016/j.cell.2010.09.049
  3. Tzadok S, Caspin Y, Hachmo Y, et al (2013). Directionality of noncoding human RNAs: how to avoid artifacts. Anal Biochem, 439, 23-9. https://doi.org/10.1016/j.ab.2013.03.031
  4. Wapinski O, Chang HY (2011). Long noncoding RNAs and human disease. Trends Cell Biol, 21, 354-61. https://doi.org/10.1016/j.tcb.2011.04.001
  5. Yamada K, Kano J, Tsunoda H, et al (2006). Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci, 97, 106-112. https://doi.org/10.1111/j.1349-7006.2006.00147.x
  6. Yang L, Lin C, Liu W, et al (2011). ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell, 147, 773-88. https://doi.org/10.1016/j.cell.2011.08.054
  7. Ying L, Chen Q, Wang Y, et al (2012). Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Bio Syst, 8, 2289-94.
  8. Zahir S, Arjmand A, Kargar S, et al (2013). Incidence and trends of malignant and benign pancreatic lesions in Yazd, Iran between 2001 and 2011. Asian Pac J Cancer Prev, 14, 2631-5. https://doi.org/10.7314/APJCP.2013.14.4.2631
  9. Zong X, Tripathi V, Prasanth KV (2011). RNA splicing control: yet another gene regulatory role for long nuclear noncoding RNAs. RNA Biol, 8, 968-77. https://doi.org/10.4161/rna.8.6.17606
  10. Shrikhande SV, Gupta S, Ostwal V (2011). Metastatic pancreatic cancer: another option? Natl Med J India, 24, 356-7.
  11. Schmidt LH, Spieker T, Koschmieder S, et al (2011). The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol, 6, 1984-92. https://doi.org/10.1097/JTO.0b013e3182307eac
  12. Schneider G, Siveke JT, Eckel F, et al (2005). Pancreatic cancer: basic and clinical aspects. Gastroenterology, 128, 1606-25. https://doi.org/10.1053/j.gastro.2005.04.001
  13. Schorderet P and Duboule D (2011). Structural and functional differences in the long non-coding RNA hotair in mouse and human. PLoS Gene, 7, 1002071. https://doi.org/10.1371/journal.pgen.1002071
  14. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  15. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  16. Siegel R, Ward E, Brawley O, et al (2011). Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 61, 212-36. https://doi.org/10.3322/caac.20121
  17. Spizzo R, Almeida MI, Colombatti A, et al (2012). Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene, 31, 4577-87. https://doi.org/10.1038/onc.2011.621
  18. Tajiri T, Tate G, Matsumoto K, et al (2012). Diagnostic challenge: intraductal neoplasms of the pancreatobiliary system. Pathol Res Prac, 208, 691-6. https://doi.org/10.1016/j.prp.2012.09.002
  19. Tang JY, Lee JC, Chang YT, et al (2013). Long noncoding RNAs-related diseases, cancers, and drugs. Scientific World J, 2013, 94359.
  20. Tano K, Akimitsu N (2012) Long non-coding RNAs in cancer progression. Front Genet, 3, 219.
  21. Mardin WA, Haier J, Mees ST (2013). Epigenetic regulation and role of metastasis suppressor genes in pancreatic ductal adenocarcinoma. BMC Cancer, 13, 264. https://doi.org/10.1186/1471-2407-13-264
  22. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  23. Lu KH, Li W, Liu XH, et al (2013). Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer, 13, 461. https://doi.org/10.1186/1471-2407-13-461
  24. Ma H, Hao Y, Dong X, et al (2012). Molecular mechanisms and function prediction of long noncoding RNA. Sci World J, 2012, 541786.
  25. Nakagawa T, Endo H, Yokoyama M, et al (2013). Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun, 436, 319-24. https://doi.org/10.1016/j.bbrc.2013.05.101
  26. Prassas I, Chrystoja CC, Makawita S, et al (2012). Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery. BMC Med, 10, 39. https://doi.org/10.1186/1741-7015-10-39
  27. Qi P, Xu MD, Ni SJ, et al (2013). Low expression of LOC285194 is associated with poor prognosis in colorectal cancer. J Transl Med, 11, 122. https://doi.org/10.1186/1479-5876-11-122
  28. Qureshi A, Hassan U, Azam M. (2011). Morphology, TNM staging and survival with pancreatico-duodenectomy specimens received at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan. Asian Pac J Cancer Prev, 12, 953-6.
  29. Ren S, Wang F, Shen J (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. https://doi.org/10.1016/j.ejca.2013.04.026
  30. Ji P, Diederichs S, Wang W, et al (2003). MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22, 8031-41. https://doi.org/10.1038/sj.onc.1206928
  31. Han Y, Liu Y, Nie L, et al (2013). Inducing cell proliferation inhibition, apoptosis, and motility reduction by silencing long noncoding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 in urothelial carcinoma of the bladder. Urology, 81, 209, 201-7.
  32. Haugk B (2010). Pancreatic intraepithelial neoplasia can we detect early pancreatic cancer? Histopathology, 57, 503-14. https://doi.org/10.1111/j.1365-2559.2010.03610.x
  33. Hutchinson JN, Ensminger AW, Clemson CM, et al (2007). A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics, 8, 39. https://doi.org/10.1186/1471-2164-8-39
  34. Ji Q, Liu X, Fu X, et al (2013). Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/beta-catenin signal pathway. PloS One, 8, 78700. https://doi.org/10.1371/journal.pone.0078700
  35. Kim K, Jutooru I, Chadalapaka G, et al (2013). HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene, 32, 1616-25. https://doi.org/10.1038/onc.2012.193
  36. Lai MC, Yang Z, Zhou L, et al (2012). Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol, 29, 1810-6 https://doi.org/10.1007/s12032-011-0004-z
  37. 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. https://doi.org/10.1038/sj.onc.1209846
  38. Liu MX, Chen X, Chen G, et al (2014). A computational framework to infer human disease-associated long noncoding RNAs. PloS One, 9, 84408. https://doi.org/10.1371/journal.pone.0084408
  39. Chen W, Wu L, Zheng R, et al (2013c). The incidences and mortalities of major cancer in China 2009. Chinese J Cancer, 32, 6.
  40. Canyilmaz E, Serdar L, Uslu GH, et al (2013). Evaluation of prognostic factors and survival results in pancreatic carcinomas in Turkey. Asian Pac J Cancer Prev, 14, 6573-8. https://doi.org/10.7314/APJCP.2013.14.11.6573
  41. Chen G, Kronenberger P, Teugels E, et al (2013a). Effect of siRNAs targeting the EGFR T790M mutation in a non-small cell lung cancer cell line resistant to EGFR tyrosine kinase inhibitors and combination with various agents. Biochem Bioph Res Commun, 431, 623-9. https://doi.org/10.1016/j.bbrc.2012.12.070
  42. Chen G, Umelo IA, Lv S, et al (2013b). miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PloS one, 8, 60317. https://doi.org/10.1371/journal.pone.0060317
  43. Consortium TEP (2007). Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature, 447, 37. https://doi.org/10.1038/447037a
  44. Guo F, Li Y, Liu Y, et al (2010). Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Bioch Bioph Sin, 42, 224-9. https://doi.org/10.1093/abbs/gmq008
  45. 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. https://doi.org/10.1038/nature08975
  46. Gutschner T, Diederichs S (2012). The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol, 9, 703-9. https://doi.org/10.4161/rna.20481
  47. Gutschner T, Hammerle M, Diederichs S (2013). MALAT1- a paradigm for long noncoding RNA function in cancer. J Mol Med, 91, 791-01. https://doi.org/10.1007/s00109-013-1028-y

Cited by

  1. Elevated expression level of long noncoding RNA MALAT-1 facilitates cell growth, migration and invasion in pancreatic cancer vol.32, pp.6, 2014, https://doi.org/10.3892/or.2014.3518
  2. Bioinformatics Method to Predict Two Regulation Mechanism: TF–miRNA–mRNA and lncRNA–miRNA–mRNA in Pancreatic Cancer vol.70, pp.3, 2014, https://doi.org/10.1007/s12013-014-0142-y
  3. Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of Gastric Cancer vol.10, pp.8, 2015, https://doi.org/10.1371/journal.pone.0135461
  4. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer vol.14, pp.1, 2015, https://doi.org/10.1186/s12943-015-0358-5
  5. Upregulation and Clinicopathological Significance of Long Non-coding NEAT1 RNA in NSCLC Tissues vol.16, pp.7, 2015, https://doi.org/10.7314/APJCP.2015.16.7.2851
  6. Long Noncoding RNAs in Digestive System Malignancies: A Novel Class of Cancer Biomarkers and Therapeutic Targets? vol.2015, pp.1687-630X, 2015, https://doi.org/10.1155/2015/319861
  7. Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis vol.21, pp.4, 2015, https://doi.org/10.1007/s12253-015-9960-5
  8. Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets vol.3, pp.1, 2015, https://doi.org/10.1186/s40591-015-0042-6
  9. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer vol.36, pp.4, 2015, https://doi.org/10.1007/s13277-014-2850-8
  10. Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma vol.36, pp.4, 2015, https://doi.org/10.1007/s13277-014-2925-6
  11. Prognostic role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 in various cancers: A meta-analysis vol.4, pp.1, 2015, https://doi.org/10.3892/mco.2015.657
  12. Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma vol.48, pp.2, 2015, https://doi.org/10.3892/ijo.2015.3292
  13. High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma vol.5, pp.1, 2015, https://doi.org/10.1038/srep12991
  14. Clinical value of lncRNA MALAT1 as a prognostic marker in human cancer: systematic review and meta-analysis vol.5, pp.9, 2015, https://doi.org/10.1136/bmjopen-2015-008653
  15. Noncoding RNAs and pancreatic cancer vol.22, pp.2, 2016, https://doi.org/10.3748/wjg.v22.i2.801
  16. Prognostic value of long noncoding RNA MALAT1 in various carcinomas: evidence from nine studies vol.37, pp.1, 2016, https://doi.org/10.1007/s13277-015-3915-z
  17. Prognostic value of long non-coding RNA MALAT1 in cancer patients vol.37, pp.1, 2016, https://doi.org/10.1007/s13277-015-3870-8
  18. Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells vol.421, pp.1-2, 2016, https://doi.org/10.1007/s11010-016-2797-8
  19. Long noncoding RNA MALAT1 can serve as a valuable biomarker for prognosis and lymph node metastasis in various cancers: a meta-analysis vol.5, pp.1, 2016, https://doi.org/10.1186/s40064-016-3342-7
  20. "Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma vol.12, pp.9, 2017, https://doi.org/10.1371/journal.pone.0184451
  21. The lncRNA MALAT1 acts as a competing endogenous RNA to regulate KRAS expression by sponging miR-217 in pancreatic ductal adenocarcinoma vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-05274-4
  22. MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis vol.14, pp.24, 2015, https://doi.org/10.1080/15384101.2015.1120917
  23. Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications vol.11, pp.3, 2016, https://doi.org/10.3892/ol.2016.4138
  24. Clinical Prognostic Value of Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Various Human Cancers: An Updated Meta-Analysis vol.31, pp.2, 2016, https://doi.org/10.5301/jbm.5000185
  25. Molecular Drivers of Pancreatic Cancer Pathogenesis: Looking Inward to Move Forward vol.18, pp.4, 2017, https://doi.org/10.3390/ijms18040779
  26. Overexpression of long noncoding RNA PEG10 promotes proliferation, invasion and metastasis of hypopharyngeal squamous cell carcinoma vol.14, pp.3, 2017, https://doi.org/10.3892/ol.2017.6498
  27. Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer vol.13, pp.2, 2018, https://doi.org/10.1371/journal.pone.0192264
  28. From biomarkers to therapeutic targets—the promises and perils of long non-coding RNAs in cancer vol.37, pp.1, 2018, https://doi.org/10.1007/s10555-017-9718-5
  29. Study on mechanism about long noncoding RNA MALAT1 affecting pancreatic cancer by regulating Hippo-YAP signaling vol.233, pp.8, 2018, https://doi.org/10.1002/jcp.26357
  30. Functions and regulatory mechanisms of metastasis-associated lung adenocarcinoma transcript 1 vol.234, pp.1, 2018, https://doi.org/10.1002/jcp.26759
  31. Clinicopathological and prognostic significance of long noncoding RNA MALAT1 in human cancers: a review and meta-analysis vol.18, pp.1, 2018, https://doi.org/10.1186/s12935-018-0606-z
  32. Interplay between regulation by methylation and noncoding RNAs in cancers pp.0959-8278, 2018, https://doi.org/10.1097/CEJ.0000000000000433
  33. Role of lncRNAs in GI Cancer vol.09, pp.03, 2018, https://doi.org/10.4236/jct.2018.93026