Display options
Cite
Ferri C, Di Biase A, Bocchetti M, et al. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res. 2022;41(1):20doi: 10.1186/s13046-021-02233-w.
Ferri, C., Di Biase, A., Bocchetti, M., Zappavigna, S., Wagner, S., Le Vu, P., Luce, A., Cossu, A. M., Vadakekolathu, J., Miles, A., Boocock, D. J., Robinson, A., Schwerdtfeger, M., Tirino, V., Papaccio, F., Caraglia, M., Regad, T., & Desiderio, V. (2022). MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. Journal of experimental & clinical cancer research : CR, 41(1), 20. https://doi.org/10.1186/s13046-021-02233-w
Ferri, Carmela, et al. "MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer." Journal of experimental & clinical cancer research : CR vol. 41,1 (2022): 20. doi: https://doi.org/10.1186/s13046-021-02233-w
Ferri C, Di Biase A, Bocchetti M, Zappavigna S, Wagner S, Le Vu P, Luce A, Cossu AM, Vadakekolathu J, Miles A, Boocock DJ, Robinson A, Schwerdtfeger M, Tirino V, Papaccio F, Caraglia M, Regad T, Desiderio V. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res. 2022 Jan 11;41(1):20. doi: 10.1186/s13046-021-02233-w. PMID: 35016717.
Copy Download .nbib Format: NLM
Share it on

J Exp Clin Cancer Res. 2022 Jan 11;41(1):20. doi: 10.1186/s13046-021-02233-w.

MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer.

Journal of experimental & clinical cancer research : CR

Carmela Ferri, Anna Di Biase, Marco Bocchetti, Silvia Zappavigna, Sarah Wagner, Pauline Le Vu, Amalia Luce, Alessia Maria Cossu, Jayakumar Vadakekolathu, Amanda Miles, David J Boocock, Alex Robinson, Melanie Schwerdtfeger, Virginia Tirino, Federica Papaccio, Michele Caraglia, Tarik Regad, Vincenzo Desiderio

Affiliations

  1. Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
  2. Medicina Futura Group, Coleman S.p.A, Via Alcide De Gasperi 107/109/111, 80011, Acerra, NA, Italy.
  3. The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK.
  4. Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031, Ariano Irpino, Italy.
  5. Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Coxford Rd, Southampton, SO16 5YA, UK.
  6. Department of Life Sciences, Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, B15 3TN, UK.
  7. Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
  8. Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Via S. Allende, 84081, Baronissi, Italy.
  9. Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy. [email protected].
  10. Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031, Ariano Irpino, Italy. [email protected].
  11. Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy. [email protected].

PMID: 35016717 DOI: 10.1186/s13046-021-02233-w

Abstract

BACKGROUND: The long non-coding RNA (lncRNA), MALAT1, plays a key role in the development of different cancers, and its expression is associated with worse prognosis in patients. However, its mechanism of action and its regulation are not well known in prostate cancer (PCa). A general mechanism of action of lncRNAs is their interaction with other epigenetic regulators including microRNAs (miRNAs).

METHODS: Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between MALAT1 and miR-423-5p, defined as a target with in silico prediction analysis, in PCa.

RESULTS: Through bioinformatic analysis of data available from TCGA, we have found that MALAT1 expression correlates with high Gleason grade, metastasis occurrence, and reduced survival in PCa patients. These findings were validated on a TMA of PCa showing a significant correlation between MALAT1 expression with both stage and grading. We report that, in PCa cells, MALAT1 expression and activity is regulated by miR-423-5p that binds MALAT1, downregulates its expression and inhibits its activity in promoting proliferation, migration, and invasion. Using NanoString analysis, we unraveled downstream cell pathways that were affected by miR-423-5p expression and MALAT1 downregulation and identified several alterations in genes that are involved in metastatic response and angiogenic pathways. In addition, we showed that the overexpression of miR-423-5p increases survival and decreases metastases formation in a xenograft mouse model.

CONCLUSIONS: We provide evidence on the role of MALAT1 in PCa tumorigenesis and progression. Also, we identify a direct interaction between miR-423-5p and MALAT1, which results in the suppression of MALAT1 action in PCa.

© 2022. The Author(s).

Keywords: Cancer; Cellular biology; Gene expression; Malat-1; Molecular biology; Prostate; lncRNAs; miR-423-5p; miRNAs

References

  1. Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009;23(13):1494–504. - PubMed
  2. Cheng W, Zhang Z, Wang J. Long noncoding RNAs: new players in prostate cancer. Cancer Lett. 2013;339(1):8–14. - PubMed
  3. Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29(4):452–63. - PubMed
  4. Kung JT, Colognori D, Lee JT. Long noncoding RNAs: past, present, and future. Genetics. 2013;193(3):651–69. - PubMed
  5. Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482(7385):339–46. - PubMed
  6. Huarte M. The emerging role of lncRNAs in cancer. Nat Med. 2015;21(11):1253–61. - PubMed
  7. Grimaldi A, Zarone MR, Irace C, Zappavigna S, Lombardi A, Kawasaki H, et al. Non-coding RNAs as a new dawn in tumor diagnosis. Semin Cell Dev Biol. 2018;78:37–50. - PubMed
  8. Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22(39):8031–41. - PubMed
  9. Gutschner T, Hammerle M, Diederichs S. MALAT1 -- a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl). 2013;91(7):791–801. - PubMed
  10. Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol. 2017;14(12):1705–14. - PubMed
  11. Wu Y, Huang C, Meng X, Li J. Long noncoding RNA MALAT1: insights into its biogenesis and implications in human disease. Curr Pharm Des. 2015;21(34):5017–28. - PubMed
  12. Zhao M, Wang S, Li Q, Ji Q, Guo P, Liu X. MALAT1: a long non-coding RNA highly associated with human cancers. Oncol Lett. 2018;16(1):19–26. - PubMed
  13. 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. - PubMed
  14. Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, et al. MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 2010;584(22):4575–80. - PubMed
  15. Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, 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. - PubMed
  16. Guo F, Li Y, Liu Y, Wang J, Li Y, Li G. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin Shanghai. 2010;42(3):224–9. - PubMed
  17. Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, et al. 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. 2011;6(12):1984–92. - PubMed
  18. Ren S, Liu Y, Xu W, Sun Y, Lu J, Wang F, et al. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol. 2013;190(6):2278–87. - PubMed
  19. Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004. - PubMed
  20. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. - PubMed
  21. Jansson MD, Lund AH. MicroRNA and cancer. Mol Oncol. 2012;6(6):590–610. - PubMed
  22. Jalali S, Bhartiya D, Lalwani MK, Sivasubbu S, Scaria V. Systematic transcriptome wide analysis of lncRNA-miRNA interactions. PLoS One. 2013;8(2):e53823. - PubMed
  23. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8. - PubMed
  24. Hao T, Wang Z, Yang J, Zhang Y, Shang Y, Sun J. MALAT1 knockdown inhibits prostate cancer progression by regulating miR-140/BIRC6 axis. Biomed Pharmacother. 2020;123:109666. - PubMed
  25. Li S, Zeng A, Hu Q, Yan W, Liu Y, You Y. miR-423-5p contributes to a malignant phenotype and temozolomide chemoresistance in glioblastomas. Neuro-Oncology. 2017;19(1):55–65. - PubMed
  26. Lin J, Huang S, Wu S, Ding J, Zhao Y, Liang L, et al. MicroRNA-423 promotes cell growth and regulates G(1)/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma. Carcinogenesis. 2011;32(11):1641–7. - PubMed
  27. Jia W, Yu T, An Q, Cao X, Pan H. MicroRNA-423-5p inhibits colon cancer growth by promoting caspase-dependent apoptosis. Exp Ther Med. 2018;16(2):1225–31. - PubMed
  28. Yang H, Fu H, Wang B, Zhang X, Mao J, Li X, et al. Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer. Mol Carcinog. 2018;57(9):1223–36. - PubMed
  29. Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, et al. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A. 2004;101(3):811–6. - PubMed
  30. Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, et al. Integrative molecular concept modeling of prostate cancer progression. Nat Genet. 2007;39(1):41–51. - PubMed
  31. Varambally S, Yu J, Laxman B, Rhodes DR, Mehra R, Tomlins SA, et al. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell. 2005;8(5):393–406. - PubMed
  32. Tomczak K, Czerwinska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol (Pozn). 2015;19(1A):A68–77. - PubMed
  33. Chen X, Wang J, Peng X, Liu K, Zhang C, Zeng X, et al. Comprehensive analysis of biomarkers for prostate cancer based on weighted gene co-expression network analysis. Medicine (Baltimore). 2020;99(14):e19628. - PubMed
  34. Liu AY, Kanan AD, Radon TP, Shah S, Weeks ME, Foster JM, et al. AGR2, a unique tumor-associated antigen, is a promising candidate for antibody targeting. Oncotarget. 2019;10(42):4276–89. - PubMed
  35. Moidu NA, Rahman N, Syafruddin SE, Low TY, Mohtar MA. Secretion of pro-oncogenic AGR2 protein in cancer. Heliyon. 2020;6(9):e05000. - PubMed
  36. Liu Q, Li A, Tian Y, Wu JD, Liu Y, Li T, et al. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016;31:61–71. - PubMed
  37. Chen X, Shao Y, Wei W, Shen H, Li Y, Chen Y, et al. Downregulation of LOX promotes castration-resistant prostate cancer progression via IGFBP3. J Cancer. 2021;12(24):7349–57. - PubMed
  38. Stiuso P, Potenza N, Lombardi A, Ferrandino I, Monaco A, Zappavigna S, et al. MicroRNA-423-5p promotes autophagy in cancer cells and is increased in serum from hepatocarcinoma patients treated with Sorafenib. Mol Ther Nucleic Acids. 2015;4:e233. - PubMed
  39. Tang X, Zeng X, Huang Y, Chen S, Lin F, Yang G, et al. miR-423-5p serves as a diagnostic indicator and inhibits the proliferation and invasion of ovarian cancer. Exp Ther Med. 2018;15(6):4723–30. - PubMed
  40. Wang X, Peng L, Gong X, Zhang X, Sun R, Du J. miR-423-5p inhibits osteosarcoma proliferation and invasion through directly targeting STMN1. Cell Physiol Biochem. 2018;50(6):2249–59. - PubMed
  41. Zhao P, Sun S, Zhai Y, Tian Q, Zhou T, Li J. miR-423-5p inhibits the proliferation and metastasis of glioblastoma cells by targeting phospholipase C beta 1. Int J Clin Exp Pathol. 2019;12(8):2941–50. - PubMed

Publication Types

Grant support