METABRIC miRNA landscape

MicroRNAs (miRNAs) are key players in cancer pathogenesis1. They display differential expression across breast cancer subtypes, and play oncogenic and tumor-suppressive roles2-6. A systematic study of the global miRNA landscape in breast cancer and the factors shaping it has not been undertaken. Here we report the results of profiling miRNA expression in 1,302 breast tumors with detailed clinical annotation and long-term follow-up, and for which matching genomic and mRNA expression data were available7. This provides a comprehensive view of the quantity, distribution and variation of the miRNA population and dissects how much genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture. The key clinical parameters and cellular pathways related to the miRNA landscape are identified, exemplified by context-dependent interaction with cell adhesion and Wnt signaling. Strikingly, in breast cancer miRNAs appear to act as modulators of mRNA-mRNA interactions rather than molecular switches. We demonstrate an important modulatory role for miRNAs in the biology of breast tumors devoid of somatic copy number aberrations, a common subtype where immune response is prominent. Remarkably, prognostic miRNA signatures derived in this subtype are consistently prognostic across several other subtypes and validate in external cohorts. These findings represent a new framework to study the biology of miRNA in human cancer.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

6 Datasets 37 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00010000434	Normalised mRNA expression	Illumina HT 12	1302
EGAD00010000436	Illumina HT 12 IDAT files	Illumina HT 12	1302
EGAD00010000438	Normalized miRNA expression data	Agilent ncRNA 60k	1480
EGAD00010000440	Segmented copy number data	Affymetrix_SNP6_raw	1302
EGAD00010000442	Affymetrix SNP 6.0 CEL files	Affymetrix_SNP6_raw	1302
EGAD00010000444	Agilent ncRNA 60k txt files	Agilent ncRNA 60k	1480

Publications	Citations
High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Leivonen SK, Sahlberg KK, Mäkelä R, Due EU, Kallioniemi O, Børresen-Dale AL, Perälä M. Mol Oncol 8: 2014 93-104	114
The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31. Viré E, Curtis C, Davalos V, Git A, Robson S, Villanueva A, Vidal A, Barbieri I, Aparicio S, Esteller M, Caldas C, Kouzarides T. Mol Cell 53: 2014 806-818	38
MicroRNA-135b regulates ERα, AR and HIF1AN and affects breast and prostate cancer cell growth. Aakula A, Leivonen SK, Hintsanen P, Aittokallio T, Ceder Y, Børresen-Dale AL, Perälä M, Östling P, Kallioniemi O. Mol Oncol 9: 2015 1287-1300	37
MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer. Xu X, Zhang Y, Jasper J, Lykken E, Alexander PB, Markowitz GJ, McDonnell DP, Li QJ, Wang XF. Oncotarget 7: 2016 20381-20394	43
The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelial-mesenchymal transition in breast cancer. Raza U, Saatci Ö, Uhlmann S, Ansari SA, Eyüpoğlu E, Yurdusev E, Mutlu M, Ersan PG, Altundağ MK, Zhang JD, Doğan HT, Güler G, Şahin Ö. Oncotarget 7: 2016 49859-49877	32
Basal-like breast cancer: molecular profiles, clinical features and survival outcomes. Milioli HH, Tishchenko I, Riveros C, Berretta R, Moscato P. BMC Med Genomics 10: 2017 19	52
Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion. Sciortino M, Camacho-Leal MDP, Orso F, Grassi E, Costamagna A, Provero P, Tam W, Turco E, Defilippi P, Taverna D, Cabodi S. Sci Rep 7: 2017 1145	11
microRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient basal-like breast cancer. Wang S, Liu JC, Ju Y, Pellecchia G, Voisin V, Wang DY, Leha L R, Ben-David Y, Bader GD, Zacksenhaus E. JCI Insight 2: 2017 93313	14
Identification of CDC25 as a Common Therapeutic Target for Triple-Negative Breast Cancer. Liu JC, Granieri L, Shrestha M, Wang DY, Vorobieva I, Rubie EA, Jones R, Ju Y, Pellecchia G, Jiang Z, Palmerini CA, Ben-David Y, Egan SE, Woodgett JR, Bader GD, Datti A, Zacksenhaus E. Cell Rep 23: 2018 112-126	36
SIK2 attenuates proliferation and survival of breast cancer cells with simultaneous perturbation of MAPK and PI3K/Akt pathways. Zohrap N, Saatci Ö, Ozes B, Coban I, Atay HM, Battaloglu E, Şahin Ö, Bugra K. Oncotarget 9: 2018 21876-21892	14
Levels of miR-126 and miR-218 are elevated in ductal carcinoma <i>in situ</i> (DCIS) and inhibit malignant potential of DCIS derived cells. Volinia S, Bertagnolo V, Grassilli S, Brugnoli F, Manfrini M, Galasso M, Scatena C, Mazzanti CM, Lessi F, Naccarato G, Caligo A, Bianchini E, Piubello Q, Orvieto E, Rugge M, Natali C, Reale D, Vecchione A, Warner S, Croce CM, Capitani S. Oncotarget 9: 2018 23543-23553	8
Screen for MicroRNA and Drug Interactions in Breast Cancer Cell Lines Points to miR-126 as a Modulator of CDK4/6 and PIK3CA Inhibitors. Baldassari F, Zerbinati C, Galasso M, Corrà F, Minotti L, Agnoletto C, Previati M, Croce CM, Volinia S. Front Genet 9: 2018 174	32
Pan-cancer characterisation of microRNA across cancer hallmarks reveals microRNA-mediated downregulation of tumour suppressors. Dhawan A, Scott JG, Harris AL, Buffa FM. Nat Commun 9: 2018 5228	67
Cholinergic Receptor Nicotinic Alpha 5 (CHRNA5) RNAi is associated with cell cycle inhibition, apoptosis, DNA damage response and drug sensitivity in breast cancer. Cingir Koker S, Jahja E, Shehwana H, Keskus AG, Konu O. PLoS One 13: 2018 e0208982	11
A subgroup of microRNAs defines PTEN-deficient, triple-negative breast cancer patients with poorest prognosis and alterations in RB1, MYC, and Wnt signaling. Wang DY, Gendoo DMA, Ben-David Y, Woodgett JR, Zacksenhaus E. Breast Cancer Res 21: 2019 18	24
Large miRNA survival analysis reveals a prognostic four-biomarker signature for triple negative breast cancer. Andrade F, Nakata A, Gotoh N, Fujita A. Genet Mol Biol 43: 2020 e20180269	11
Molecular stratification within triple-negative breast cancer subtypes. Wang DY, Jiang Z, Ben-David Y, Woodgett JR, Zacksenhaus E. Sci Rep 9: 2019 19107	66
Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Saatci O, Kaymak A, Raza U, Ersan PG, Akbulut O, Banister CE, Sikirzhytski V, Tokat UM, Aykut G, Ansari SA, Dogan HT, Dogan M, Jandaghi P, Isik A, Gundogdu F, Kosemehmetoglu K, Dizdar O, Aksoy S, Akyol A, Uner A, Buckhaults PJ, Riazalhosseini Y, Sahin O. Nat Commun 11: 2020 2416	133
Association of germline variation with the survival of women with <i>BRCA1/2</i> pathogenic variants and breast cancer. Muranen TA, Khan S, Fagerholm R, Aittomäki K, Cunningham JM, Dennis J, Leslie G, McGuffog L, Parsons MT, Simard J, Slager S, Soucy P, Easton DF, Tischkowitz M, Spurdle AB, kConFab Investigators, Schmutzler RK, Wappenschmidt B, Hahnen E, Hooning MJ, HEBON Investigators, Singer CF, Wagner G, Thomassen M, Pedersen IS, Domchek SM, Nathanson KL, Lazaro C, Rossing CM, Andrulis IL, Teixeira MR, James P, Garber J, Weitzel JN, SWE-BRCA Investigators, Jakubowska A, Yannoukakos D, John EM, Southey MC, Schmidt MK, Antoniou AC, Chenevix-Trench G, Blomqvist C, Nevanlinna H. NPJ Breast Cancer 6: 2020 44	3
MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer. Petrelli A, Bellomo SE, Sarotto I, Kubatzki F, Sgandurra P, Maggiorotto F, Di Virgilio MR, Ponzone R, Geuna E, Galizia D, Nuzzo AM, Medico E, Miglio U, Berrino E, Venesio T, Ribisi S, Provero P, Sapino A, Giordano S, Montemurro F. ESMO Open 5: 2020 e000937	8
Aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector, fuels breast cancer cell proliferation. Canu V, Donzelli S, Sacconi A, Lo Sardo F, Pulito C, Bossel N, Di Benedetto A, Muti P, Botti C, Domany E, Bicciato S, Strano S, Yarden Y, Blandino G. Cell Death Differ 28: 2021 1493-1511	14
Construction of a MicroRNA-Based Nomogram for Prediction of Lung Metastasis in Breast Cancer Patients. Zhang L, Pan J, Wang Z, Yang C, Huang J. Front Genet 11: 2020 580138	5
Uncovering the roles of microRNAs/lncRNAs in characterising breast cancer subtypes and prognosis. Li X, Truong B, Xu T, Liu L, Li J, Le TD. BMC Bioinformatics 22: 2021 300	3
High miR-30 Expression Associates with Improved Breast Cancer Patient Survival and Treatment Outcome. Jamshidi M, Fagerholm R, Muranen TA, Kaur S, Potdar S, Khan S, Netti E, Mpindi JP, Yadav B, Kiiski JI, Aittomäki K, Heikkilä P, Saarela J, Bützow R, Blomqvist C, Nevanlinna H. Cancers (Basel) 13: 2021 2907	3
Accurate prediction of breast cancer survival through coherent voting networks with gene expression profiling. Pellegrini M. Sci Rep 11: 2021 14645	2
Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB. Nagalingam A, Siddharth S, Parida S, Muniraj N, Avtanski D, Kuppusamy P, Elsey J, Arbiser JL, Győrffy B, Sharma D. NPJ Breast Cancer 7: 2021 105	9
Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways. Amirfallah A, Knutsdottir H, Arason A, Hilmarsdottir B, Johannsson OT, Agnarsson BA, Barkardottir RB, Reynisdottir I. PLoS One 16: 2021 e0260327	15
miR-101-5p Acts as a Tumor Suppressor in HER2-Positive Breast Cancer Cells and Improves Targeted Therapy. Normann LS, Haugen MH, Aure MR, Kristensen VN, Mælandsmo GM, Sahlberg KK. Breast Cancer (Dove Med Press) 14: 2022 25-39	6
Multiomics Topic Modeling for Breast Cancer Classification. Valle F, Osella M, Caselle M. Cancers (Basel) 14: 2022 1150	4
5'isomiR-183-5p\|+2 elicits tumor suppressor activity in a negative feedback loop with E2F1. Li X, Michels BE, Tosun OE, Jung J, Kappes J, Ibing S, Nataraj NB, Sahay S, Schneider M, Wörner A, Becki C, Ishaque N, Feuerbach L, Heßling B, Helm D, Will R, Yarden Y, Müller-Decker K, Wiemann S, Körner C. J Exp Clin Cancer Res 41: 2022 190	3
miR-489 Confines Uncontrolled Estrogen Signaling through a Negative Feedback Mechanism and Regulates Tamoxifen Resistance in Breast Cancer. Soni M, Saatci O, Gupta G, Patel Y, Keerthi Raja MR, Li J, Liu X, Xu P, Wang H, Fan D, Sahin O, Chen H. Int J Mol Sci 23: 2022 8086	2
Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of gene regulatory programs in cancers. Castro-Mondragon JA, Aure MR, Lingjærde OC, Langerød A, Martens JWM, Børresen-Dale AL, Kristensen VN, Mathelier A. Nucleic Acids Res 50: 2022 12131-12148	4
Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification. Saatci O, Akbulut O, Cetin M, Sikirzhytski V, Uner M, Lengerli D, O'Quinn EC, Romeo MJ, Caliskan B, Banoglu E, Aksoy S, Uner A, Sahin O. Cell Death Differ 30: 2023 1305-1319	7
spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape. Boniolo F, Hoffmann M, Roggendorf N, Tercan B, Baumbach J, Castro MAA, Robertson AG, Saur D, List M. Bioinformatics 39: 2023 btad276	5
CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer. Shrestha M, Wang DY, Ben-David Y, Zacksenhaus E. Oncogenesis 12: 2023 29	2
In Silico Identification of a BRCA1:miR-29:DNMT3 Axis Involved in the Control of Hormone Receptors in BRCA1-Associated Breast Cancers. Santarosa M, Baldazzi D, Armellin M, Maestro R. Int J Mol Sci 24: 2023 9916	0
CRISPR screens in 3D tumourspheres identified miR-4787-3p as a transcriptional start site miRNA essential for breast tumour-initiating cell growth. Stiff T, Bayraktar S, Dama P, Stebbing J, Castellano L. Commun Biol 7: 2024 859	0