Objective: Breast Cancer (BC) is characterized by high complexity and
heterogeneity, and microRNA (miRNA) is bound up with the occurrence and development of BC. In this study, we evaluated the
prognostic value of miRNA in BC. Background: Breast ductal and lobular cancers are the most common types of Breast
Carcinomas (BC) and indicate the high complexity heterogeneity in this disease.
Each BC patient has unique morphological and molecular
features. MicroRNAs (miRNAs) play a critical role in human oncogenesis, progression, and prognosis. Our study aimed
to identify potential prognostic biomarkers of breast ductal and lobular
cancers to predict the overall survival
outcome. Methods: All analyzed miRNA sequencing and clinical data
were obtained from the Genomic Data Commons Data Porta. edgeR package in R software was used to analyze the differential
miRNA expression profiles. Complete
survival information and differentially expressed miRNA expression were
obtained and the Caret package was used for random division of the samples
along with their profiles into two groups (training group and test group). We performed univariate Cox regression analyses for
miRNAs in the traininggroup.
We utilized three different web-based tools to identify the target genes of miRNAs and used the Perl language
to evaluate the target genes for miRNA
signature. STRING database was used to assess PPIs.
References
[1]
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660
[2]
Vachhani, H., Shah, P.A., Robila, V. and Idowu, M.O. (2018) Invasive Carcinomas, Diagnosis and Management of Breast Tumors. 191-232.
https://doi.org/10.1007/978-3-319-57726-5_9
[3]
Luque-Bolivar, A., Perez-Mora, E., Villegas, V.E. and Rondón-Lagos, M. (2020) Resistance and Overcoming Resistance in Breast Cancer. Breast Cancer, 12, 211-229.
https://doi.org/10.2147/BCTT.S270799
[4]
Schnitt, S.J. (2010) Classification and Prognosis of Invasive Breast Cancer: From Morphology to Molecular Taxonomy. Modern Pathology, 23, S60-S64.
https://doi.org/10.1038/modpathol.2010.33
[5]
Ha, M. and Kim, V.N. (2014) Regulation of microRNA Biogenesis. Nature Reviews Molecular Cell Biology, 15, 509-524. https://doi.org/10.1038/nrm3838
[6]
Fernandez-Valdivia, R., Takeuchi, H., Samarghandi, A., Lopez, M., Leonardi, J., Haltiwanger, R.S. and Jafar-Nejad, H. (2011) Regulation of Mammalian Notch Signaling and Embryonic Development by the Protein O-Glucosyltransferase Rumi. Development, 138, 1925-1934. https://doi.org/10.1242/dev.060020
[7]
Calin, G.A. and Croce, C.M. (2006) MicroRNA Signatures in Human Cancers. Nature Reviews Cancer, 6, 857-866. https://doi.org/10.1038/nrc1997
[8]
Heagerty, P.J., Lumley, T. and Pepe, M.S. (2000) Time-Dependent ROC Curves for Censored Survival Data and a Diagnostic Marker. Biometrics, 56, 337-344.
https://doi.org/10.1111/j.0006-341X.2000.00337.x
[9]
Shi, S., Lu, Y., Qin, Y., Li, W., Cheng, H., Xu, Y., Xu, J., Long, J., Liu, L., Liu, C. and Yu, X. (2014) miR-1247 Is Correlated with Prognosis of Pancreatic Cancer and Inhibits Cell Proliferation by Targeting Neuropilins. Current Molecular Medicine, 14, 316-327.
https://doi.org/10.2174/1566524014666140228120014
[10]
Siegel, R.L., Miller, K.D. and Jemal, A. (2020) Cancer Statistics, 2020. CA: A Cancer Journal for Clinicians, 70, 7-30. https://doi.org/10.3322/caac.21590
[11]
Desantis, C.E., Fedewa, S.A., Sauer, A.G., Kramer, J.L., Smith, R.A. and Jemal, A. (2016) Breast Cancer Statistics, 2015: Convergence of Incidence Rates between Black and White Women. CA: A Cancer Journal for Clinicians, 66, 31-42.
https://doi.org/10.3322/caac.21320
[12]
Li, Z. and Kang, Y. (2016) Emerging Therapeutic Targets in Metastatic Progression: A Focus on Breast Cancer. Pharmacology & Therapeutics, 161, 79-96.
https://doi.org/10.1016/j.pharmthera.2016.03.003
[13]
Temian, D.C., Pop, L.A., Irimie, A.I. and Berindan-Neagoe, I. (2018) The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge. Journal of Breast Cancer, 21, 233-243. https://doi.org/10.4048/jbc.2018.21.e41
[14]
Loh, H.Y., Norman, B.P., Lai, K.S., Rahman, N.M.A.N.A., Alitheen, N.B.M. and Osman, M.A. (2019) The Regulatory Role of MicroRNAs in Breast Cancer. International Journal of Molecular Sciences, 20, E4940.
https://doi.org/10.3390/ijms20194940
[15]
Shen, Z., Chai, T., Luo, F., Liu, Z., Xu, H., Zhang, P., Kang, M. and Chen, S. (2020) Loss of miR-204-5p Promotes Tumor Proliferation, Migration, and Invasion through Targeting YWHAZ/PI3K/AKT Pathway in Esophageal Squamous Cell Carcinoma. OncoTargets and Therapy, 13, 4679-4690. https://doi.org/10.2147/OTT.S243215
[16]
Luan, W., Qian, Y., Ni, X., Bu, X.F., Xia, Y., Wang, J.L., Ruan, H.R., Ma, S.J. and Xu, B. (2017) miR-204-5p Acts as a Tumor Suppressor by Targeting Matrix Metalloproteinases-9 and B-Cell Lymphoma-2 in Malignant Melanoma. OncoTargets and Therapy, 10, 1237-1246. https://doi.org/10.2147/OTT.S128819
[17]
Chu, Y., Jiang, M., Du, F., Chen, D., Ye, T., Xu, B., Li, X., Wang, W., Qiu, Z., Liu, H., Nie, Y., Liang, J. and Fan, D. (2018) miR-204-5p Suppresses Hepatocellular Cancer Proliferation by Regulating Homeoprotein SIX1 Expression. FEBS Open Bio, 8, 189-200. https://doi.org/10.1002/2211-5463.12363
[18]
Wang, F., Dai, M., Chen, H., et al. (2018) Prognostic Value of Hsa-mir-299 and Hsamir-7706 in Hepatocellular Carcinoma. Oncology Letters, 16, 815-820.
https://doi.org/10.3892/ol.2018.8710
[19]
Scaravilli, M., Porkka, K.P., Brofeldt, A., et al. (2015) MiR-1247-5p Is Overexpressed in Castration Resistant Prostate Cancer and Targets MYCBP2. Prostate, 75, 798-805.
https://doi.org/10.1002/pros.22961
[20]
Zhao, F., Lv, J., Gan, H., et al. (2015) MiRNA Profile of Osteosarcoma with CD117 and Stro-1 Expression: miR-1247 Functions as an onco-miRNA by Targeting MAP3K9. International Journal of Clinical and Experimental Pathology, 8, 1451-1458.
[21]
Fang, T., Lv, H., Lv, G., et al. (2018) Tumor-Derived Exosomal miR-1247-3p Induces Cancer-Associated Fibroblast Activation to Foster Lung Metastasis of Liver Cancer. Nature Communications, 9, 191. https://doi.org/10.1038/s41467-017-02583-0
[22]
Li, D., Ilnytskyy, Y., Kovalchuk, A., et al. (2013) Crucial Role for Early Growth Response-1 in the Transcriptional Regulation of miR-20b in Breast Cancer. Oncotarget, 4, 1373-1387. https://doi.org/10.18632/oncotarget.1165
[23]
Cascio, S., D’andrea, A., Ferla, R., et al. (2010) miR-20b Modulates VEGF Expression by Targeting HIF-1 Alpha and STAT3 in MCF-7 Breast Cancer Cells. Journal of Cellular Physiology, 224, 242-249. https://doi.org/10.1002/jcp.22126
[24]
Huang, T., Alvarez, A.A., Pangeni, R.P., et al. (2016) A Regulatory Circuit of miR-125b/miR-20b and Wnt Signalling Controls Glioblastoma Phenotypes through FZD6-Modulated Pathways. Nature Communications, 7, 12885.
https://doi.org/10.1038/ncomms12885
[25]
So, A.Y., Zhao, J.L. and Baltimore, D. (2013) The Yin and Yang of microRNAs: Leukemia and Immunity. Immunological Reviews, 253, 129-145.
https://doi.org/10.1111/imr.12043
[26]
Liao, Y., Cao, L., Wang, F., et al. (2020) miR-605-5p Promotes Invasion and Proliferation by Targeting TNFAIP3 in Non-Small-Cell Lung Cancer. Journal of Cellular Biochemistry, 121, 779-787. https://doi.org/10.1002/jcb.29323
[27]
Lu, R., Zhang, X., Li, X., et al. (2020) Circ_0016418 Promotes Melanoma Development and Glutamine Catabolism by Regulating the miR-605-5p/GLS Axis. International Journal of Clinical and Experimental Pathology, 13, 1791-1801.
[28]
Lei, B., Wang, D., Zhang, M., et al. (2020) miR-615-3p Promotes the Epithelial-Mesenchymal Transition and Metastasis of Breast Cancer by Targeting PICK1/TGFBRI Axis. Journal of Experimental & Clinical Cancer Research, 39, 71.
https://doi.org/10.1186/s13046-020-01571-5
[29]
Santoni, G., Morelli, M.B., Marinelli, O., et al. (2020) Calcium Signaling and the Regulation of Chemosensitivity in Cancer Cells: Role of the Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, 1131, 505-517.
https://doi.org/10.1007/978-3-030-12457-1_20
[30]
Wei, J., Hu, M., Huang, K., et al. (2020) Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression. International Journal of Molecular Sciences, 21, 5983. https://doi.org/10.3390/ijms21175983
[31]
Asl, E.R., Amini, M., Najafi, S., et al. (2021) Interplay between MAPK/ERK Signaling Pathway and MicroRNAs: A Crucial Mechanism Regulating Cancer Cell Metabolism and Tumor Progression. Life Sciences, 278, Article ID: 119499.
https://doi.org/10.1016/j.lfs.2021.119499
[32]
Xu, S., Zhang, H., Liu, T., et al. (2019) G Protein Gamma Subunit 7 Loss Contributes to Progression of Clear Cell Renal Cell Carcinoma. Journal of Cellular Physiology, 234, 20002-20012. https://doi.org/10.1002/jcp.28597
[33]
Santamaria, D., Barriere, C., Cerqueira, A., et al. (2007) Cdk1 Is Sufficient to Drive the Mammalian Cell Cycle. Nature, 448, 811-815.
https://doi.org/10.1038/nature06046
[34]
Lim, S. and Kaldis, P. (2013) Cdks, Cyclins and CKIs: Roles beyond Cell Cycle Regulation. Development, 140, 3079-3093. https://doi.org/10.1242/dev.091744
[35]
Malumbres, M. and Barbacid, M. (2009) Cell Cycle, CDKs and Cancer: A Changing Paradigm. Nature Reviews Cancer, 9, 153-166. https://doi.org/10.1038/nrc2602
[36]
Thompson, D.M. and Gill, G.N. (1985) The EGF Receptor: Structure, Regulation and Potential Role in Malignancy. Journal of Cancer Survivorship, 4, 767-788.
[37]
Li, F., Aljahdali, I. and Ling, X. (2019) Cancer Therapeutics Using Survivin BIRC5 as a Target: What Can We Do after over Two Decades of Study? Journal of Experimental & Clinical Cancer Research, 38, 368. https://doi.org/10.1186/s13046-019-1362-1
[38]
Dustin, D., Gu, G. and Fuqua, S.W. (2019) ESR1 Mutations in Breast Cancer. Cancer, 125, 3714-3728. https://doi.org/10.1002/cncr.32345
[39]
Han, W., Carpenter, R.L., Cao, X., et al. (2013) STAT1 Gene Expression Is Enhanced by Nuclear EGFR and HER2 via Cooperation with STAT3. Molecular Carcinogenesis, 52, 959-969. https://doi.org/10.1002/mc.21936
[40]
Wang, Y., Chang, H., Rattner, A., et al. (2016) Frizzled Receptors in Development and Disease. Current Topics in Developmental Biology, 117, 113-139.
https://doi.org/10.1016/bs.ctdb.2015.11.028
[41]
Wei, L., Diao, Y., Qi, J., et al. (2013) Effect of Change in Spindle Structure on Proliferation Inhibition of Osteosarcoma Cells and Osteoblast under Simulated Microgravity during Incubation in Rotating Bioreactor. PLoS ONE, 8, e76710.
https://doi.org/10.1371/journal.pone.0076710
[42]
Sun, C., Huang, S., Ju, W., et al. (2018) Elevated DSN1 Expression Is Associated with Poor Survival in Patients with Hepatocellular Carcinoma. Human Pathology, 81, 113-120. https://doi.org/10.1016/j.humpath.2018.06.032
[43]
Kline, S.L., Cheeseman, I.M., Hori, T., et al. (2006) The Human Mis12 Complex Is Required for Kinetochore Assembly and Proper Chromosome Segregation. Journal of Cell Biology, 173, 9-17. https://doi.org/10.1083/jcb.200509158
[44]
Gilman, A.G. (1987) G Proteins: Transducers of Receptor-Generated Signals. Annual Review of Biochemistry, 56, 615-649.
https://doi.org/10.1146/annurev.bi.56.070187.003151
[45]
Simon, M.I., Strathmann, M.P. and Gautam, N. (1991) Diversity of G Proteins in Signal Transduction. Science, 252, 802-808. https://doi.org/10.1126/science.1902986
[46]
Parekh, H.K., Adikari, M. and Vennapusa, B. (2006) Differential Partitioning of Galphai1 with the Cellular Microtubules: A Possible Mechanism of Development of Taxol Resistance in Human Ovarian Carcinoma Cells. Journal of Molecular Signaling, 1, 3.
https://doi.org/10.1186/1750-2187-1-3
[47]
Ram, P.T. and Iyengar, R. (2001) G Protein Coupled Receptor Signaling through the Src and Stat3 Pathway: Role in Proliferation and Transformation. Oncogene, 20, 1601-1606. https://doi.org/10.1038/sj.onc.1204186
[48]
Taussig, R., Iñiguez-Lluhi, J.A. and Gilman, A.G. (1993) Inhibition of Adenylyl Cyclase by Gi Alpha. Science, 261, 218-221. https://doi.org/10.1126/science.8327893
[49]
Seo, M., Nam, H.J., Kim, S.Y., et al. (2009) Inhibitory Heterotrimeric GTP-Binding Proteins Inhibit Hydrogen Peroxide-Induced Apoptosis by Up-Regulation of Bcl-2 via NF-kappaB in H1299 Human Lung Cancer Cells. Biochemical and Biophysical Research Communications, 381, 153-158. https://doi.org/10.1016/j.bbrc.2009.01.188
[50]
Embry, A.C., Glick, J.L., Linder, M.E., et al. (2004) Reciprocal Signaling between the Transcriptional Co-Factor Eya2 and Specific Members of the Galphai Family. Molecular Pharmacology, 66, 1325-1331. https://doi.org/10.1124/mol.104.004093