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Dysregulation of non-histone molecule miR205 and LRG1 post-transcriptional de-regulation by SETD1A in triple negative breast cancer

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Abstract

FEC chemo-resistance in triple negative breast cancer (TNBC) remains a challenge. Therefore it is crucial to determine the right treatment regime by understanding molecular mechanisms of driver regulators involved in the progression of TNBCs. This study aims to understand SETD1A mechanisms in TNBC development in two TNBC cell lines. SETD1A was transiently transfected in MDA-MB-468 (FEC good prognosis) and Hs578T (FEC poor prognosis). Regulation of potential targets miR205, EMT marker ZEB1 and LRG1 and proliferative marker Ki-67 were tested by RqPCR to elucidate SETD1A interactions. This study displayed significant recovery of miR205 with SETD1A depletion and reduction of ZEB1 in MDA-MB-468. However, ZEB1 remained unchanged in Hs578T indicating ZEB1 regulation may be outcompeted by other mechanisms associated with aggressive cell line characteristics and the expression of endogenous ZEB1 was relatively high in Hs578T. Elevation of LRG1 and declined Ki-67 were observed by SETD1A knocked down. Enhanced expression was observed by LRG1 in Hs578T and not in MDA-MB-468 suggesting LRG1 contributed to distinct poor FEC outcome in TNBCs. The underlying mechanism of SETD1A in miR205/ZEB1/Ki-67/LRG1 axis needs further evaluation. Whether abrogation of the pathway is indeed associated with transcriptional or post-transcriptional activation in TNBC cell lines models, clearly validation in clinical samples is warranted to achieve its prognostic and therapeutic values in TNBCs.

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References

  1. Stockmans G, Deraedt K, Wildiers H, Moerman P, Paridaens R (2008) Triple-negative breast cancer. Curr Opin Oncol 20:614–620

    Article  PubMed  Google Scholar 

  2. Gasco M, Shami S, Crook T (2002) The p53 pathway in breast cancer. Breast Cancer Res 4:70–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Willis A, Jung EJ, Wakefield T, Chen X (2004) Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes. Oncogene 23:2330–2338

    Article  CAS  PubMed  Google Scholar 

  4. Turner N, Moretti E, Siclari O, Migliaccio I, Santarpia L, D’Incalci M, Piccolo S, Veronesi A, Zambelli A, Del Sal G, Di Leo A (2013) Targeting triple negative breast cancer: is p53 the answer? Cancer Treat Rev 39:541–550

    Article  CAS  PubMed  Google Scholar 

  5. Muller PAJ, Trinidad AG, Caswell PT, Norman JC, Vousden KH (2014) Mutant p53 regulates dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. J Biol Chem 289:122–132

    Article  CAS  PubMed  Google Scholar 

  6. Bertucci F, Finetti P, Rougemont J, Charafe-Jauffret E, Cervera N, Tarpin C, Nguyen C, Xerri L, Houlgatte R, Jacquemier J, Viens P, Birnbaum D (2005) Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. Cancer Res 65:2170–2178

    Article  CAS  PubMed  Google Scholar 

  7. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig 121:2750–2767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe J-P, Tong F, Speed T, Spellman PT, DeVries S, Lapuk A, Wang NJ, Kuo W-L, Stilwell JL, Pinkel D, Albertson DG, Waldman FM, McCormick F, Dickson RB, Johnson MD, Lippman M, Ethier S, Gazdar A, Gray JW (2006) A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10:515–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Anders CK, Winer EP, Ford JM, Dent R, Silver DP, Sledge W, Carey LA, Carolina N, Hill C, Inhibition PARP (2011) “Targeted” therapy for triple negative breast cancer. Clin Cancer Res 16:4702–4710

    Article  CAS  Google Scholar 

  10. Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26:1275–1281

    Article  PubMed  Google Scholar 

  11. Baxter E, Windloch K, Gannon F, Lee JS (2014) Epigenetic regulation in cancer development. Cell Biosci 4:1–11

    Article  CAS  Google Scholar 

  12. Peña-Chilet M, Martínez MT, Pérez-Fidalgo JA, Peiró-Chova L, Oltra SS, Tormo E, Alonso-Yuste E, Martinez-Delgado B, Eroles P, Climent J, Burgués O, Ferrer-Lozano J, Bosch A, Lluch A, Ribas G (2014) MicroRNA profile in very young women with breast cancer. BMC Cancer 14:529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu L, Kimball S, Liu H, Holowatyj A, Yang Z-Q (2015) Genetic alterations of histone lysine methyltransferases and their significance in breast cancer. Oncotarget 6:2466–2482

    PubMed  Google Scholar 

  14. Salz T, Deng C, Pampo C, Siemann D, Qiu Y, Brown K, Huang S (2014) Histone methyltransferase hSETD1A is a novel regulator of metastasis in breast cancer. Mol Cancer Res 13:461–469

    Article  CAS  PubMed  Google Scholar 

  15. Salz TH (2014) Novel roles for human SETD1A histone methyltransferase in regulation of canonical WNT signaling pathway, cellular proliferation and metastasis

  16. Cheng X, Sun S, Zhong F, He K, Zhou J (2016) Knockdown of histone methyltransferase hSETD1A inhibits progression, migration, and invasion in human hepatocellular carcinoma. Oncol Res Featur Preclin Clin Cancer Ther 24:239–245

    Google Scholar 

  17. Hanif EA, Mullan PB, Kennedy R (2015) MiR205 is a p53/p63-dependent marker lost in poor outcome triple negative breast cancers. Eur J Cancer Care 24:24–82

    Google Scholar 

  18. Mayoral-Varo V, Calcabrini A, Sánchez-Bailón MP, Martín-Pérez J (2017) miR205 inhibits stem cell renewal in SUM159PT breast cancer cells. PLoS ONE 12:1–14

    Article  CAS  Google Scholar 

  19. Vrba L, Garbe JC, Stampfer MR, Futscher BW (2011) Epigenetic regulation of normal human mammary cell type-specific miRNAs. Genome Res 21:2026–2037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kathryn JC, Sireesha G, Stanley VL (2012) Triple negative breast cancer cell lines: one tool in the search for better treatment of triple negative breast cancer. Breast Dis 32:35–48

    Google Scholar 

  21. Akagi I, Miyashita M, Ishibashi O, Mishima T, Kikuchi K, Makino H, Nomura T, Hagiwara N, Uchida E, Takizawa T (2011) Relationship between altered expression levels of MIR21, MIR143, MIR145, and MIR205 and clinicopathologic features of esophageal squamous cell carcinoma. Dis Esophagus 24:523–530

    Article  CAS  PubMed  Google Scholar 

  22. Gyorffy B, Surowiak P, Budczies J, Lanczky A (2013) Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS ONE 8:1–8

    Article  CAS  Google Scholar 

  23. Piovan C, Palmieri D, Di Leva G, Braccioli L, Casalini P, Nuovo G, Tortoreto M, Sasso M, Plantamura I, Triulzi T, Taccioli C, Tagliabue E, Iorio MV, Croce CM (2012) Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer. Mol Oncol 6:458–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang Z, Liao H, Deng Z, Yang P, Du N, Zhanng Y, Ren H (2013) miRNA-205 affects infiltration and metastasis of breast cancer. Biochem Biophys Res Commun 441:139–143

    Article  CAS  PubMed  Google Scholar 

  25. Zhang Y, Luo Q, Wang N, Hu F, Jin H, Ge T, Wang C, Qin W (2015) LRG1 suppresses the migration and invasion of hepatocellular carcinoma cells. Med Oncol 32:1–10

    Article  CAS  Google Scholar 

  26. Xie ZB, Zhang YF, Jin C, Mao YS, Fu DL (2019) LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling. J Exp Clin Cancer Res 38:1–12

    Article  Google Scholar 

  27. Radojicic J, Zaravinos A, Vrekoussis T, Kafousi M, Spandidos DA, Stathopoulos EN (2011) MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer. Cell Cycle 10:507–517

    Article  CAS  PubMed  Google Scholar 

  28. Gupta I, Sareyeldin RM, Al-Hashimi I, Al-Thawadi HA, Al Farsi H, Vranic S, Al Moustafa AE (2019) Triple negative breast cancer profile, from gene to microRNA, in relation to ethnicity. Cancers (Basel) 11:1–25

    CAS  Google Scholar 

  29. Bhatnagar N, Li X, Padi SKR, Zhang Q, Tang MS, Guo B (2010) Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells. Cell Death Dis 1:1–8

    Article  CAS  Google Scholar 

  30. Mohamad Hanif EA, Shah SA (2018) Overview on epigenetic re-programming: a potential therapeutic intervention in triple negative breast cancers. Asian Pac J Cancer Prev 19:3341–3351

    Article  PubMed  Google Scholar 

  31. Bianchi M, Renzini A, Adamo S, Moresi V (2017) Coordinated actions of microRNAs with other epigenetic factors regulate skeletal muscle development and adaptation. Int J Mol Sci 18:1–14

    Google Scholar 

  32. Geretto M, Pulliero A, Rosano C, Zhabayeva D, Bersimbaev R, Izzotti A (2017) Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators. Am J Cancer Res 7:1350–1371

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Tao B-B, Liu X-Q, Zhang W, Li S, Dong D, Xiao M, Zhong J (2017) Evidence for the association of chromatin and microRNA regulation in the human genome. Oncotarget 8:70958–70966

    PubMed  PubMed Central  Google Scholar 

  34. Gurtan AM, Ravi A, Rahl PB, Bosson AD, Jnbaptiste CK, Bhutkar A, Whittaker CA, Young RA, Sharp PA (2013) Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts. Genes Dev 27:941–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gosline SJC, Gurtan AM, Jnbaptiste CK, Bosson A, Milani P, Dalin S, Matthews BJ, Yap YS, Sharp PA, Fraenkel E (2016) Elucidating microRNA regulatory networks using transcriptional, post-transcriptional and histone modification measurements. Cell Rep 14:310–319

    Article  CAS  PubMed  Google Scholar 

  36. Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH, Muller PAJ, Dotsch V, Kehrloesser S, Sayan BS, Giaccone G, Lowe SW, Takahashi N, Vandenabeele P, Knight RA, Levine AJ, Melino G (2012) Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. PNAS 109:15312–15317

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zhang P, Wang L, Rodriguea-Aguayo C, Yuan Y, Debeb BG, Chen D, You MJ, Liu Y, Dean DC, Woodward WA, Liang H, Lopez-Berestein G, Sood AK, Hu Y, Ang KK, Chen J, Ma L (2015) MiR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13. J Chem Inf Model 5:5671

    Google Scholar 

  38. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601

    Article  CAS  PubMed  Google Scholar 

  39. Banin Hirata BK, Oda JMM, Losi Guembarovski R, Ariza CB, de Oliveira CEC, Watanabe MAE (2014) Molecular markers for breast cancer: prediction on tumor behavior. Dis Markers. 2014:513158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhou F, Li S, Meng H-M, Qi L-Q, Gu L (2013) MicroRNA and histopathological characterization of pure mucinous breast carcinoma. Cancer Biol Med 10:22–27

    PubMed  PubMed Central  Google Scholar 

  41. Kamalakaran S, Varadan V, Giercksky Russnes HE, Levy D, Kendall J, Janevski A, Riggs M, Banerjee N, Synnestvedt M, Schlichting E, Kåresen R, Shama Prasada K, Rotti H, Rao R, Rao L, Eric Tang M-H, Satyamoorthy K, Lucito R, Wigler M, Dimitrova N, Naume B, Borresen-Dale A-L, Hicks JB (2011) DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables. Mol Oncol 5:77–92

    Article  CAS  PubMed  Google Scholar 

  42. Lehmann BD, Pietenpol JA (2015) Clinical implications of molecular heterogeneity in triple negative breast cancer. Breast 24(Suppl 2):S36–S40

    Article  PubMed  Google Scholar 

  43. Wu J, Yin H, Zhu J, Buckanovich RJ, Thorpe JD, Dai J, Urban N, Lubman DM (2015) Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study. PLoS ONE 10:1–11

    Google Scholar 

  44. Ramirez-Ardila DE, Ruigrok-Ritstier K, Helmijr JC, Look MP, van Laere S, Dirix L, Berns EMJJ, Jansen MPHM (2016) LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome. Mol Oncol 10:1363–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was funded by Geran Galakan Penyelidik Muda (Young Investigator Grant) (Project Code: GGPM-2017-103).

Funding

This study was funded by Geran Galakan Penyelidik Muda (Young Investigator Grant) (Project Code: GGPM-2017-103).

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  1. UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia Medical Centre, Jalan Ya’acob Latiff, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia

    Ezanee Azlina Mohamad Hanif

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Correspondence to Ezanee Azlina Mohamad Hanif.

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Mohamad Hanif, E.A. Dysregulation of non-histone molecule miR205 and LRG1 post-transcriptional de-regulation by SETD1A in triple negative breast cancer. Mol Biol Rep 46, 6617–6624 (2019). https://doi.org/10.1007/s11033-019-05079-w

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