Skip to main content
Top
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Research

miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1

Published in: Molecular Cancer | Issue 1/2017

Login to get access

Abstract

Background

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. T-cell intracellular antigen 1 (TIA1) is an important tumor suppressor involved in many aspects of carcinogenesis and cancer development. How TIA1 expression is regulated during CRC development remains to be carefully elucidated.

Methods

In CRC tissue sample pairs, TIA1 protein and mRNA levels were monitored by Western blot and qRT-PCR, respectively. Combining meta-analysis and miRNA target prediction software, we could predict microRNAs that targeted TIA1. Next, three CRC cell lines (SW480, Caco2 and HT29) were used to demonstrate the direct targeting of TIA1 by miR-19a. In addition, we investigated the biological effects of TIA1 inhibition by miR-19a both in vitro by CCK-8, EdU, Transwell, Ki67 immunofluorescence and Colony formation assays and in vivo by a xenograft mice model.

Results

In colorectal cancer (CRC), we found that TIA1 protein, but not its mRNA, was downregulated. We predicted that TIA1 was a target of miR-19a and validated that miR-19a binded directly to the 3’-UTR of TIA1 mRNA. miR-19a could promote cell proliferation and migration in CRC cells and accelerated tumor growth in xenograft mice by targeting TIA1.

Conclusions

This study highlights an oncomiR role for miR-19a in regulating TIA1 in CRC and suggests that miR-19a may be a novel molecular therapeutic target for CRC.

Literature
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.View ArticlePubMed
  2. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–60.View ArticlePubMedPubMed Central
  3. Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P. Smoking and colorectal cancer: a meta-analysis. JAMA. 2008;300:2765–78.View ArticlePubMed
  4. Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT, Lancet Physical Activity Series Working G. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012;380:219–29.View ArticlePubMedPubMed Central
  5. Zoratto F, Rossi L, Verrico M, Papa A, Basso E, Zullo A, Tomao L, Romiti A, Lo Russo G, Tomao S. Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis. Tumour Biol. 2014;35:6195–206.View ArticlePubMed
  6. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3:11–22.View ArticlePubMed
  7. Su J, Liang H, Yao W, Wang N, Zhang S, Yan X, Feng H, Pang W, Wang Y, Wang X, et al. MiR-143 and MiR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer. PLoS One. 2014;9, e114420.View ArticlePubMedPubMed Central
  8. Dow LE, O'Rourke KP, Simon J, Tschaharganeh DF, van Es JH, Clevers H, Lowe SW. Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer. Cell. 2015;161:1539–52.View ArticlePubMedPubMed Central
  9. Liu Y, Uzair Ur R, Guo Y, Liang H, Cheng R, Yang F, Hong Y, Zhao C, Liu M, Yu M, et al. miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4. Protein Cell. 2016;7:722–34.View ArticlePubMedPubMed Central
  10. Sanchez-Jimenez C, Izquierdo JM. T-cell intracellular antigens in health and disease. Cell Cycle. 2015;14:2033–43.View ArticlePubMedPubMed Central
  11. Tian Q, Streuli M, Saito H, Schlossman SF, Anderson P. A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell. 1991;67:629–39.View ArticlePubMed
  12. Reyes R, Alcalde J, Izquierdo JM. Depletion of T-cell intracellular antigen proteins promotes cell proliferation. Genome Biol. 2009;10:R87.View ArticlePubMedPubMed Central
  13. Kawai T, Lal A, Yang X, Galban S, Mazan-Mamczarz K, Gorospe M. Translational control of cytochrome c by RNA-binding proteins TIA-1 and HuR. Mol Cell Biol. 2006;26:3295–307.View ArticlePubMedPubMed Central
  14. Izquierdo JM, Alcalde J, Carrascoso I, Reyes R, Ludena MD. Knockdown of T-cell intracellular antigens triggers cell proliferation, invasion and tumour growth. Biochem J. 2011;435:337–44.View ArticlePubMed
  15. Hamdollah Zadeh MA, Amin EM, Hoareau-Aveilla C, Domingo E, Symonds KE, Ye X, Heesom KJ, Salmon A, D'Silva O, Betteridge KB, et al. Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance. Mol Oncol. 2015;9:167–78.View ArticlePubMedPubMed Central
  16. Zlobec I, Karamitopoulou E, Terracciano L, Piscuoglio S, Iezzi G, Muraro MG, Spagnoli G, Baker K, Tzankov A, Lugli A. TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. PLoS One. 2010;5, e14282.View ArticlePubMedPubMed Central
  17. Izquierdo JM, Majos N, Bonnal S, Martinez C, Castelo R, Guigo R, Bilbao D, Valcarcel J. Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. Mol Cell. 2005;19:475–84.View ArticlePubMed
  18. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.View ArticlePubMed
  19. Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol. 2007;23:175–205.View ArticlePubMed
  20. Orom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 2008;30:460–71.View ArticlePubMed
  21. Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature. 2008;455:1124–8.View ArticlePubMed
  22. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.View ArticlePubMed
  23. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.View ArticlePubMed
  24. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.View ArticlePubMed
  25. Johnston RJ, Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 2003;426:845–9.View ArticlePubMed
  26. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.View ArticlePubMed
  27. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.View ArticlePubMed
  28. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005;65:9628–32.View ArticlePubMed
  29. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.View ArticlePubMedPubMed Central
  30. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet. 2006;38:1060–5.View ArticlePubMedPubMed Central
  31. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008;132:875–86.View ArticlePubMedPubMed Central
  32. Huang L, Wang X, Wen C, Yang X, Song M, Chen J, Wang C, Zhang B, Wang L, Iwamoto A, et al. Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-alpha induced epithelial-to-mesenchymal transition in colorectal cancer. Sci Rep. 2015;5:13350.View ArticlePubMed
  33. Zhang J, Xiao Z, Lai D, Sun J, He C, Chu Z, Ye H, Chen S, Wang J. miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer. Br J Cancer. 2012;107:352–9.View ArticlePubMedPubMed Central
  34. Cellura D, Pickard K, Quaratino S, Parker H, Strefford JC, Thomas GJ, Mitter R, Mirnezami AH, Peake NJ. miR-19-Mediated Inhibition of Transglutaminase-2 Leads to Enhanced Invasion and Metastasis in Colorectal Cancer. Mol Cancer Res. 2015;13:1095–105.View ArticlePubMedPubMed Central
  35. Naito S, von Eschenbach AC, Giavazzi R, Fidler IJ. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986;46:4109–15.PubMed
  36. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.View ArticlePubMed
  37. Cheng WC, Chung IF, Huang TS, Chang ST, Sun HJ, Tsai CF, Liang ML, Wong TT, Wang HW. YM500: a small RNA sequencing (smRNA-seq) database for microRNA research. Nucleic Acids Res. 2013;41:D285–294.View ArticlePubMed
  38. Cheng WC, Chung IF, Tsai CF, Huang TS, Chen CY, Wang SC, Chang TY, Sun HJ, Chao JY, Cheng CC, et al. YM500v2: a small RNA sequencing (smRNA-seq) database for human cancer miRNome research. Nucleic Acids Res. 2015;43:D862–867.View ArticlePubMed
  39. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–98.View ArticlePubMed
  40. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS Biol. 2004;2, e363.View ArticlePubMedPubMed Central
  41. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N. Combinatorial microRNA target predictions. Nat Genet. 2005;37:495–500.View ArticlePubMed
  42. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.View ArticlePubMed
  43. Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013;20:1603–14.View ArticlePubMedPubMed Central
  44. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839–43.View ArticlePubMed
  45. Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B, Meijer GA. MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer. 2009;101:707–14.View ArticlePubMedPubMed Central
  46. Wigington CP, Jung J, Rye EA, Belauret SL, Philpot AM, Feng Y, Santangelo PJ, Corbett AH. Post-transcriptional regulation of programmed cell death 4 (PDCD4) mRNA by the RNA-binding proteins human antigen R (HuR) and T-cell intracellular antigen 1 (TIA1). J Biol Chem. 2015;290:3468–87.View ArticlePubMed
  47. Corte H, Manceau G, Blons H, Laurent-Puig P. MicroRNA and colorectal cancer. Dig Liver Dis. 2012;44:195–200.View ArticlePubMed
  48. Mazeh H, Mizrahi I, Ilyayev N, Halle D, Brucher B, Bilchik A, Protic M, Daumer M, Stojadinovic A, Itzhak A, Nissan A. The Diagnostic and Prognostic Role of microRNA in Colorectal Cancer - a Comprehensive review. J Cancer. 2013;4:281–95.View ArticlePubMedPubMed Central
  49. Brunet Vega A, Pericay C, Moya I, Ferrer A, Dotor E, Pisa A, Casalots A, Serra-Aracil X, Oliva JC, Ruiz A, Saigi E. microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising biomarkers. Oncol Rep. 2013;30:320–6.PubMed
  50. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137:1005–17.View ArticlePubMedPubMed Central
  51. Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010;28:341–7.View ArticlePubMedPubMed Central
  52. Xu P, Zhu Y, Sun B, Xiao Z. Colorectal cancer characterization and therapeutic target prediction based on microRNA expression profile. Sci Rep. 2016;6:20616.View ArticlePubMedPubMed Central
  53. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005;438:685–9.View ArticlePubMed
  54. Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, Cordon-Cardo C, Li QJ, Lowe SW, Hannon GJ, He L. miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 2009;23:2839–49.View ArticlePubMedPubMed Central
  55. Feng Y, Liu J, Kang Y, He Y, Liang B, Yang P, Yu Z. miR-19a acts as an oncogenic microRNA and is up-regulated in bladder cancer. J Exp Clin Cancer Res. 2014;33:67.View ArticlePubMedPubMed Central
  56. Xu XM, Wang XB, Chen MM, Liu T, Li YX, Jia WH, Liu M, Li X, Tang H. MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5. Cancer Lett. 2012;322:148–58.View ArticlePubMed
  57. Lu WD, Zuo Y, Xu Z, Zhang M. MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer. World J Gastroenterol. 2015;21:4564–73.PubMedPubMed Central
  58. Tan Y, Yin H, Zhang H, Fang J, Zheng W, Li D, Li Y, Cao W, Sun C, Liang Y, et al. Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer. Oncotarget. 2015;6:17391–403.View ArticlePubMedPubMed Central
  59. Xiao W, Gao Z, Duan Y, Yuan W, Ke Y. Downregulation of miR-19a exhibits inhibitory effects on metastatic renal cell carcinoma by targeting PIK3CA and inactivating Notch signaling in vitro. Oncol Rep. 2015;34:739–46.PubMed
  60. Hu W, Jin P, Ding C, Liu W. miR-19a/b modulates lung cancer cells metastasis through suppression of MXD1 expression. Oncol Lett. 2016;12:1901–5.PubMedPubMed Central
  61. Dang CV. MYC on the path to cancer. Cell. 2012;149:22–35.View ArticlePubMedPubMed Central
  62. Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005;6:635–45.View ArticlePubMed
  63. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science. 1998;281:1509–12.View ArticlePubMed
  64. Pelengaris S, Khan M, Evan GI. Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell. 2002;109:321–34.View ArticlePubMed
  65. Psathas JN, Thomas-Tikhonenko A. MYC and the art of microRNA maintenance. Cold Spring Harb Perspect Med. 2014;4.
  66. Frenzel A, Loven J, Henriksson MA. Targeting MYC-Regulated miRNAs to Combat Cancer. Genes Cancer. 2010;1:660–7.View ArticlePubMedPubMed Central
  67. Liao B, Hu Y, Brewer G. Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nat Struct Mol Biol. 2007;14:511–8.View ArticlePubMed
  68. Gottschald OR, Malec V, Krasteva G, Hasan D, Kamlah F, Herold S, Rose F, Seeger W, Hanze J. TIAR and TIA-1 mRNA-binding proteins co-aggregate under conditions of rapid oxygen decline and extreme hypoxia and suppress the HIF-1alpha pathway. J Mol Cell Biol. 2010;2:345–56.View ArticlePubMed
  69. Dixon DA, Balch GC, Kedersha N, Anderson P, Zimmerman GA, Beauchamp RD, Prescott SM. Regulation of cyclooxygenase-2 expression by the translational silencer TIA-1. J Exp Med. 2003;198:475–81.View ArticlePubMedPubMed Central
  70. Sanchez-Jimenez C, Carrascoso I, Barrero J, Izquierdo JM. Identification of a set of miRNAs differentially expressed in transiently TIA-depleted HeLa cells by genome-wide profiling. BMC Mol Biol. 2013;14:4.View ArticlePubMedPubMed Central
Metadata
Title
miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1
Publication date
01-12-2017
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0625-8

Other articles of this Issue 1/2017

Molecular Cancer 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine