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UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis

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Tumor Biology

Abstract

Urothelial cancer associated 1 (UCA1) is an example of functional long noncoding RNAs involved in many biologic processes. However, little is known about the association between UCA1 expression and metastasis in epithelial ovarian cancer (EOC). Findings of this study confirmed that not only UCA1 was aberrantly upregulated in EOC tissues and cells, but also correlated with status of lymph node metastasis and FIGO stage. Furthermore, univariate and multivariate analyses showed that UCA1 was a prognostic factor for overall survival in EOC patients. In vitro, knockdown of UCA1 reduced the invasion and migration ability of EOC cells. The results showed that UCA1 could function as an endogenous sponge by directly binding to miR-485-5p. Depletion of UCA1 was involved in the downregulation of matrix metallopeptidase 14 (MMP14) expression, a target gene of miR-485-5p. In conclusion, our work indicates that UCA1 is a new prognostic biomarker for EOC, establishing a novel connection among UCA1, miR-485-5p, and MMP14 in EOC metastasis.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29. doi:10.3322/caac.21254.

    Article  PubMed  Google Scholar 

  2. Bast Jr RC, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9(6):415–28. doi:10.1038/nrc2644.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bowtell DDL. The genesis and evolution of high-grade serous ovarian cancer. Nat Rev Cancer. 2010;10(11):803–8. doi:10.1038/nrc2946.

    Article  CAS  PubMed  Google Scholar 

  4. Rustin G, van der Burg M, Griffin C, Qian W, Swart AM. Early versus delayed treatment of relapsed ovarian cancer. Lancet. 2011;377(9763):380–1. doi:10.1016/s0140-6736(11)60126-8.

    Article  PubMed  Google Scholar 

  5. Tsai M-C, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;71(1):3–7. doi:10.1158/0008-5472.can-10-2483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Huang J-L, Zheng L, Hu Y-W, Wang Q. Characteristics of long non-coding RNA and its relation to hepatocellular carcinoma. Carcinogenesis. 2014;35(3):507–14. doi:10.1093/carcin/bgt405.

    Article  CAS  PubMed  Google Scholar 

  7. Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15(1):7–21. doi:10.1038/nrg3606.

    Article  CAS  PubMed  Google Scholar 

  8. J-j Q, Lin Y-y, L-c Y, J-x D, W-w F, H-y J, et al. Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol. 2014;134(1):121–8. doi:10.1016/j.ygyno.2014.03.556.

    Article  Google Scholar 

  9. Sheng X, Li J, Yang L, Chen Z, Zhao Q, Tan L, et al. Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer. Oncol Rep. 2014;32(1):277–85. doi:10.3892/or.2014.3208.

    CAS  PubMed  Google Scholar 

  10. Qiu J-J, Lin Y-Y, Ding J-X, Feng W-W, Jin H-Y, Hua K-Q. Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer. Int J Oncol. 2015;46(6):2497–505. doi:10.3892/ijo.2015.2943.

    CAS  PubMed  Google Scholar 

  11. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147(2):358–69. doi:10.1016/j.cell.2011.09.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kallen AN, Zhou X-B, Xu J, Qiao C, Ma J, Yan L, et al. The imprinted H19 LncRNA antagonizes Let-7 MicroRNAs. Mol Cell. 2013;52(1):101–12. doi:10.1016/j.molcel.2013.08.027.

    Article  CAS  PubMed  Google Scholar 

  13. Wang K, Long B, Zhou L-Y, Liu F, Zhou Q-Y, Liu C-Y, et al. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun. 2014;5:3596. doi:10.1038/ncomms4596.

    PubMed  Google Scholar 

  14. Wang F, Li X, Xie X, Zhao L, Chen W. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 2008;582(13):1919–27. doi:10.1016/j.febslet.2008.05.012.

    Article  CAS  PubMed  Google Scholar 

  15. Wang T, Yuan J, Feng N, Li Y, Lin Z, Jiang Z, et al. Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer. Tumor Biol. 2014;35(10):10075–84. doi:10.1007/s13277-014-2321-2.

    Article  CAS  Google Scholar 

  16. Li Z, Li X, Wu S, Xue M, Chen W. Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway. Cancer Sci. 2014;105(8):951–5. doi:10.1111/cas.12461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang F, Zhou J, Xie X, Hu J, Chen L, Hu Q, et al. Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1 in human ovarian cancer cells. Neoplasma. 2015;62(3):432–8. doi:10.4149/neo_2015_051.

    Article  CAS  PubMed  Google Scholar 

  18. Fu WM, Zhu X, Wang WM, Lu YF, Hu BG, Wang H, et al. Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling. J Hepatol. 2015;63(4):886–95. doi:10.1016/j.jhep.2015.05.016.

    Article  CAS  PubMed  Google Scholar 

  19. Kim TH, Kim YK, Kwon Y, Heo JH, Kang H, Kim G, et al. Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours. Histopathology. 2010;57(5):734–43. doi:10.1111/j.1365-2559.2010.03686.x.

    Article  PubMed  Google Scholar 

  20. Izaurralde E. Elucidating the temporal order of silencing. EMBO Rep. 2012;13(8):662–3. doi:10.1038/embor.2012.91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102–14. doi:10.1038/nrg2290.

    Article  CAS  PubMed  Google Scholar 

  22. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123(4):631–40. doi:10.1016/j.cell.2005.10.022.

    Article  CAS  PubMed  Google Scholar 

  23. X-h L, Sun M, Nie F-q, Ge Y-b, Zhang E-b, Yin D-d, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92. doi:10.1186/1476-4598-13-92.

    Article  Google Scholar 

  24. Wang F, Ying H-Q, He B-S, Pan Y-Q, Deng Q-W, Sun H-L, et al. Upregulated IncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget. 2015;6(10):7899–917.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M, et al. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis. 2014;5:e1008. doi:10.1038/cddis.2013.541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. H-m Z, Yang F-q, Chen S-J, Che J, Zheng J-h. Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumor Biol. 2015;36(4):2947–55. doi:10.1007/s13277-014-2925-6.

    Article  Google Scholar 

  27. Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. Plos Genet. 2013;9(3):e1003368. doi:10.1371/journal.pgen.1003368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pang E-J, Yang R, Fu X-b, Liu Y-f. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumor Biol. 2015;36(4):2403–7. doi:10.1007/s13277-014-2850-8.

    Article  CAS  Google Scholar 

  29. Anaya-Ruiz M, Bandala C, Perez-Santos JL. miR-485 acts as a tumor suppressor by inhibiting cell growth and migration in breast carcinoma T47D cells. Asian Pac J Cancer Prev. 2013;14(6):3757–60.

    Article  PubMed  Google Scholar 

  30. He N, Zheng H, Li P, Zhao Y, Zhang W, Song F, et al. miR-485-5p binding site SNP rs8752 in HPGD gene is associated with breast cancer risk. PLoS One. 2014;9(7):e102093. doi:10.1371/journal.pone.0102093.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pahwa S, Stawikowski MJ, Fields GB. Monitoring and inhibiting MT1-MMP during cancer initiation and progression. Cancers. 2014;6(1):416–35. doi:10.3390/cancers6010416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jo Y, Yeon J, Kim HJ, Lee ST. Analysis of tissue inhibitor of metalloproteinases-2 effect on pro-matrix metalloproteinase-2 activation by membrane-type 1 matrix metalloproteinase using baculovirus/insect-cell expression system. Biochem J. 2000;345(Pt 3):511–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang Y-z, Wu K-p, Wu A-b, Yang Z-c, J-m L, Y-l M, et al. MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer. Tumor Biol. 2014;35(10):9815–21. doi:10.1007/s13277-014-2237-x.

    Article  CAS  Google Scholar 

  34. Udayakumar TS, Chen ML, Bair EL, von Bredow DC, Cress AE, Nagle RB, et al. Membrane type-1-matrix metalloproteinase expressed by prostate carcinoma cells cleaves human laminin-5 beta 3 chain and induces cell migration. Cancer Res. 2003;63(9):2292–9.

    CAS  PubMed  Google Scholar 

  35. Munaut C, Noel A, Hougrand O, Foidart JM, Boniver J, Deprez M. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Int J Cancer. 2003;106(6):848–55. doi:10.1002/ijc.11313.

    Article  CAS  PubMed  Google Scholar 

  36. Wang L, Yuan J, Tu Y, Mao X, He S, Fu G, et al. Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma. Clin Transl Oncol. 2013;15(2):139–45. doi:10.1007/s12094-012-0900-5.

    Article  CAS  PubMed  Google Scholar 

  37. Albrechtsen R, Kveiborg M, Stautz D, Vikesa J, Noer JB, Kotzsh A, et al. ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis and increased tumor growth. J Cell Sci. 2013;126(Pt 20):4707–20. doi:10.1242/jcs.129510.

    Article  CAS  PubMed  Google Scholar 

  38. Yang C, Li X, Wang Y, Zhao L, Chen W. Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through P13-K dependent pathway in bladder carcinoma cells. Gene. 2012;496(1):8–16. doi:10.1016/j.gene.2012.01.012.

    Article  CAS  PubMed  Google Scholar 

  39. Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteomics Bioinformatics. 2009;7(4):147–54. doi:10.1016/s1672-0229(08)60044-3.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Jinsong Liu (University of Texas M.D. Anderson Cancer Center) for revising the manuscript carefully. This work was supported by the National Nature Science Foundation of China (81472442, 81272871), Jiangsu Province Medical Key Talent Grant (2011).

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Correspondence to Wenjun Cheng.

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Yang, Y., Jiang, Y., Wan, Y. et al. UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis. Tumor Biol. 37, 10633–10641 (2016). https://doi.org/10.1007/s13277-016-4917-1

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  • DOI: https://doi.org/10.1007/s13277-016-4917-1

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