Skip to main content
NCBI home page
Cancer Biomarkers: Section A of Disease Markers logoLink to Cancer Biomarkers: Section A of Disease Markers
. 2017 May 6;19(1):75–83. doi: 10.3233/CBM-160376

LncRNA, NEAT1 is a prognosis biomarker and regulates cancer progression via epithelial-mesenchymal transition in clear cell renal cell carcinoma

Li Ning a,*, Zhiguo Li a, Dianjun Wei a, Haiyan Chen b, Chao Yang c
PMCID: PMC13020697  PMID: 28269753

Abstract

BACKGROUND:

The long non-coding RNAs (lncRNAs) are emerging as important regulators in cancer progression. Clear cell renal cell carcinoma (ccRCC) is one of the most common urological cancers with poor prognosis. In this study, we examined the functional role of the lncRNA, nuclear enriched abundant transcript 1 (NEAT1) in ccRCC progression.

METHODS:

We performed quantitative real time PCR and western blotting assays to measure mRNA and protein expression levels, respectively. CCK-8 assay, cell invasion and migration assays were used to determine the cell proliferative, cell invasive and migratory ability. Flow cytometric analysis was performed to examine cell apoptosis.

RESULTS:

The expression levels of NEAT1 was up-regulated in ccRCC tissues and up-regulation of NETA1 was positively correlated with tumor size, higher Fuhrman grade, and lymph node metastasis, and also predicts worse 5-year survival rate of patients with ccRCC. NEAT1 knock-down by NEAT siRNAs transfection suppressed cell proliferation and induced cell apoptosis in ccRCC cell lines. In addition, NEAT1 knock-down suppressed cell invasion and migration and inhibited the mRNA and protein expression levels of epithelial-mesenchymal transition-related markers in ccRCC cell lines.

CONCLUSIONS:

In conclusion, NEAT1 may be an important mediator in the regulation of ccRCC progression and predicts the poor prognosis in patients with ccRCC.

Keywords: lncRNA, ccRCC, NEAT1, epithelial-mesenchymal transition, progression, prognosis

References

  • [1]. Ljungberg B., Campbell S.C., Choi H.Y., Jacqmin D., Lee J.E., Weikert S. and Kiemeney L.A., The epidemiology of renal cell carcinoma, Eur Urol 60 (2011), 615-21. [DOI] [PubMed] [Google Scholar]
  • [2]. Pal S.K. and Figlin R.A., Targeted therapies for renal cell carcinoma: Understanding their impact on survival, Target Oncol 5 (2010), 131-8. [DOI] [PubMed] [Google Scholar]
  • [3]. Porta C. and Szczylik C., Tolerability of first-line therapy for metastatic renal cell carcinoma, Cancer Treat Rev 35 (2009), 297-307. [DOI] [PubMed] [Google Scholar]
  • [4]. Van Poppel H., Becker F., Cadeddu J.A., Gill I.S., Janetschek G., Jewett M.A., Laguna M.P., Marberger M., Montorsi F., Polascik T.J., Ukimura O. and Zhu G., Treatment of localised renal cell carcinoma, Eur Urol 60 (2011), 662-72. [DOI] [PubMed] [Google Scholar]
  • [5]. Yagoda A., Abi-Rached B. and Petrylak D., Chemotherapy for advanced renal-cell carcinoma: 1983-1993, Semin Oncol 22 (1995), 42-60. [PubMed] [Google Scholar]
  • [6]. Bartonicek N., Maag J.L. and Dinger M.E., Long noncoding RNAs in cancer: Mechanisms of action and technological advancements, Mol Cancer 15 (2016), 43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7]. Bhan A. and Mandal S.S., LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer, Biochim Biophys Acta 1856 (2015), 151-64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8]. Gutschner T., Hammerle M. and Diederichs S., MALAT1 - a paradigm for long noncoding RNA function in cancer, J Mol Med (Berl) 91 (2013), 791-801. [DOI] [PubMed] [Google Scholar]
  • [9]. Yao J., Chen Y., Wang Y., Liu S., Yuan X., Pan F. and Geng P., Decreased expression of a novel lncRNA CADM1-AS1 is associated with poor prognosis in patients with clear cell renal cell carcinomas, Int J Clin Exp Pathol 7 (2014), 2758-67. [PMC free article] [PubMed] [Google Scholar]
  • [10]. Zhang H.M., Yang F.Q., Chen S.J., Che J. and Zheng J.H., Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma, Tumour Biol 36 (2015), 2947-55. [DOI] [PubMed] [Google Scholar]
  • [11]. Wu Y., Tan C., Weng W.W., Deng Y., Zhang Q.Y., Yang X.Q., Gan H.L., Wang T., Zhang P.P., Xu M.D., Wang Y.Q. and Wang C.F., Long non-coding RNA Linc00152 is a positive prognostic factor for and demonstrates malignant biological behavior in clear cell renal cell carcinoma, Am J Cancer Res 6 (2016), 285-99. [PMC free article] [PubMed] [Google Scholar]
  • [12]. Souquere S., Beauclair G., Harper F., Fox A. and Pierron G., Highly ordered spatial organization of the structural long noncoding NEAT1 RNAs within paraspeckle nuclear bodies, Mol Biol Cell 21 (2010), 4020-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13]. Chen Z.J., Zhang Z., Xie B.B. and Zhang H.Y., Clinical significance of up-regulated lncRNA NEAT1 in prognosis of ovarian cancer, Eur Rev Med Pharmacol Sci 20 (2016), 3373-7. [PubMed] [Google Scholar]
  • [14]. Fu J.W., Kong Y. and Sun X., Long noncoding RNA NEAT1 is an unfavorable prognostic factor and regulates migration and invasion in gastric cancer, J Cancer Res Clin Oncol 142 (2016), 1571-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15]. Lo P.K., Zhang Y., Wolfson B., Gernapudi R., Yao Y., Duru N. and Zhou Q., Dysregulation of the BRCA1/long non-coding RNA NEAT1 signaling axis contributes to breast tumorigenesis, Oncotarget (2016). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16]. Sun C., Li S., Zhang F., Xi Y., Wang L., Bi Y. and Li D., Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway, Oncotarget (2016). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17]. XianGuo C., ZongYao H., Jun Z., Song F., GuangYue L., LiGang Z., KaiPing Z., YangYang Z. and ChaoZhao L., Promoting progression and clinicopathological significance of NEAT1 over-expression in bladder cancer, Oncotarget (2016). [Google Scholar]
  • [18]. Wu Y., Lyu H., Liu H., Shi X., Song Y. and Liu B., Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer, Sci Rep 6 (2016), 31093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19]. Chakravarty D., Sboner A., Nair S.S., Giannopoulou E., Li R., Hennig S., Mosquera J.M., Pauwels J., Park K., Kossai M., MacDonald T.Y., Fontugne J., Erho N., Vergara I.A., Ghadessi M., Davicioni E., Jenkins R.B., Palanisamy N., Chen Z., Nakagawa S., Hirose T., Bander N.H., Beltran H., Fox A.H., Elemento O. and Rubin M.A., The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer, Nat Commun 5 (2014), 5383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20]. Guo S., Chen W., Luo Y., Ren F., Zhong T., Rong M., Dang Y., Feng Z. and Chen G., Clinical implication of long non-coding RNA NEAT1 expression in hepatocellular carcinoma patients, Int J Clin Exp Pathol 8 (2015), 5395-402. [PMC free article] [PubMed] [Google Scholar]
  • [21]. Wu Y., Yang L., Zhao J., Li C., Nie J., Liu F., Zhuo C., Zheng Y., Li B., Wang Z. and Xu Y., Nuclear-enriched abundant transcript 1 as a diagnostic and prognostic biomarker in colorectal cancer, Mol Cancer 14 (2015), 191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22]. Xu H., He L., Feng X., Kapoor A. and Tang D., Specific reduction of fas-associated protein with death domain (FADD) in clear cell renal cell carcinoma, Cancer Invest 27 (2009), 836-43. [DOI] [PubMed] [Google Scholar]
  • [23]. Blume C.J., Hotz-Wagenblatt A., Hullein J., Sellner L., Jethwa A., Stolz T., Slabicki M., Lee K., Sharathchandra A., Benner A., Dietrich S., Oakes C.C., Dreger P., te Raa D., Kater A.P., Jauch A., Merkel O., Oren M., Hielscher T. and Zenz T., p53-dependent non-coding RNA networks in chronic lymphocytic leukemia, Leukemia 29 (2015), 2015-23. [DOI] [PubMed] [Google Scholar]
  • [24]. Diepenbruck M. and Christofori G., Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol 43 (2016), 7-13. [DOI] [PubMed] [Google Scholar]
  • [25]. Peinado H. and Cano A., New potential therapeutic targets to combat epithelial tumor invasion, Clin Transl Oncol 8 (2006), 851-7. [DOI] [PubMed] [Google Scholar]
  • [26]. Gotzmann J., Mikula M., Eger A., Schulte-Hermann R., Foisner R., Beug H. and Mikulits W., Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis, Mutat Res 566 (2004), 9-20. [DOI] [PubMed] [Google Scholar]
  • [27]. Hemavathy K., Ashraf S.I. and Ip Y.T., Snail/slug family of repressors: slowly going into the fast lane of development and cancer, Gene 257 (2000), 1-12. [DOI] [PubMed] [Google Scholar]
  • [28]. Liu Y., El-Naggar S., Darling D.S., Higashi Y. and Dean D.C., Zeb1 links epithelial-mesenchymal transition and cellular senescence, Development 135 (2008), 579-88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [29]. Lu Y., Li T., Wei G., Liu L., Chen Q., Xu L., Zhang K., Zeng D. and Liao R., The long non-coding RNA NEAT1 regulates epithelial to mesenchymal transition and radioresistance in through miR-204/ZEB1 axis in nasopharyngeal carcinoma, Tumour Biol (2016). [DOI] [PubMed] [Google Scholar]
  • [30]. Xiong J., Liu Y., Jiang L., Zeng Y. and Tang W., High expression of long non-coding RNA lncRNA-ATB is correlated with metastases and promotes cell migration and invasion in renal cell carcinoma, Jpn J Clin Oncol 46 (2016), 378-84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31]. Mlcochova H., Machackova T., Rabien A., Radova L., Fabian P., Iliev R., Slaba K., Poprach A., Kilic E., Stanik M., Redova-Lojova M., Svoboda M., Dolezel J., Vyzula R., Jung K. and Slaby O., Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma, Sci Rep 6 (2016), 31852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32]. Li X., Wang S., Li Z., Long X., Guo Z., Zhang G., Zu J., Chen Y. and Wen L., NEAT1 induces epithelial-mesenchymal transition and 5-FU resistance through the miR-129/ZEB2 axis in breast cancer, FEBS Lett (2016). [DOI] [PubMed] [Google Scholar]
  • [33]. Lu Y., Li T., Wei G., Liu L., Chen Q., Xu L., Zhang K., Zeng D. and Liao R., The long non-coding RNA NEAT1 regulates epithelial to mesenchymal transition and radioresistance in through miR-204/ZEB1 axis in nasopharyngeal carcinoma, Tumour Biol 37 (2016), 11733-11741. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Biomarkers: Section A of Disease Markers are provided here courtesy of SAGE Publications

RESOURCES