Blood-based MicroRNA Profiling Unveils Complex Molecular Dynamics in Breast Cancer

Overview

Journal J Appl Genet

Publisher Springer

Specialty Genetics

Date 2024 Mar 13

PMID 38478327

Authors

Mudassar Shahid

Rabbani Syed

M A Ansari

Gowher Shafi

James John

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer, a genetically intricate disease with diverse subtypes, exhibits heightened incidence globally. In this study, we aimed to investigate blood-based microRNAs (miRNAs) as potential biomarkers for breast cancer. The primary objectives were to explore the role of miRNAs in cancer-related processes, assess their differential expression between breast cancer patients and healthy individuals, and contribute to a deeper understanding of the molecular underpinnings of breast cancer.

Methods: MiRNA extraction was performed on 40 breast cancer patients and adjacent normal tissues using a commercial RNA isolation kit. Total RNA quantification and quality assessment were conducted with advanced technologies. MiRNA profiling involved reverse transcription, labeling, and hybridization on Agilent human miRNA arrays (V2). Bioinformatics analysis utilized the DIANA system for target gene prediction and the DIANA-mirPath tool for pathway enrichment analysis. Selected miRNAs underwent validation through quantitative real-time PCR.

Results: Principal component analysis revealed overlapping miRNA expression patterns in primary and malignant breast tumors, underscoring the genetic complexity involved. Statistical analysis identified 54 downregulated miRNAs in malignant tumors and 38 in primary tumors compared to controls. Bioinformatics analysis implicated several pathways, including Wnt, TGF-b, ErbB, and MAPK signaling. Validation through qRT-PCR confirmed altered expression of hsa-miR-130a, hsa-miR-21, hsa-miR-223, and hsa-let-7c key miRNAs, highlighting their significance in breast cancer. The results from microarray were further validated by qPCR and the expression of which are downregulated in breast cancer was detected.

Conclusion: This study provides significant insights into distinct miRNA expression patterns in normal and malignant breast tissues. The overlapping miRNA profiles in primary and malignant tumors underscore the complexity of genetic regulation in breast cancer. The identification of deregulated miRNAs and affected pathways contributes to our understanding of breast cancer pathogenesis. The validated miRNAs hold potential as diagnostic and prognostic markers, offering avenues for further clinical exploration in breast cancer research.

Citing Articles

Unveiling miRNA30b's Role in Suppressing ADAM12 to Combat Triple-Negative Breast Cancer.

Yin Q, Hu J, Zhou Q, Weng J, Shen E, Wen F Breast J. 2025; 2024:5202941.

PMID: 39742357 PMC: 11540880. DOI: 10.1155/2024/5202941.

References

Al Tamimi D, Shawarby M, Ahmed A, Hassan A, Alodaini A . Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study. BMC Cancer. 2010; 10:223. PMC: 2880995. DOI: 10.1186/1471-2407-10-223. View

Al-Foheidi M, Al-Mansour M, Ibrahim E . Breast cancer screening: review of benefits and harms, and recommendations for developing and low-income countries. Med Oncol. 2013; 30(2):471. DOI: 10.1007/s12032-013-0471-5. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Calin G, Sevignani C, Dumitru C, Hyslop T, Noch E, Yendamuri S . Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004; 101(9):2999-3004. PMC: 365734. DOI: 10.1073/pnas.0307323101. View

Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y . Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009; 28(10):1385-92. DOI: 10.1038/onc.2008.474. View

Di Leva G, Croce C . miRNA profiling of cancer. Curr Opin Genet Dev. 2013; 23(1):3-11. PMC: 3632255. DOI: 10.1016/j.gde.2013.01.004. View

Farazi T, Horlings H, Ten Hoeve J, Mihailovic A, Halfwerk H, Morozov P . MicroRNA sequence and expression analysis in breast tumors by deep sequencing. Cancer Res. 2011; 71(13):4443-53. PMC: 3129492. DOI: 10.1158/0008-5472.CAN-11-0608. View

Forouzanfar M, Foreman K, Delossantos A, Lozano R, Lopez A, Murray C . Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011; 378(9801):1461-84. DOI: 10.1016/S0140-6736(11)61351-2. View

Frankel L, Christoffersen N, Jacobsen A, Lindow M, Krogh A, Lund A . Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2007; 283(2):1026-33. DOI: 10.1074/jbc.M707224200. View

10.

Guo L, Zhao Y, Yang S, Cai M, Wu Q, Chen F . Genome-wide screen for aberrantly expressed miRNAs reveals miRNA profile signature in breast cancer. Mol Biol Rep. 2012; 40(3):2175-86. DOI: 10.1007/s11033-012-2277-5. View

11.

Hanahan D, Weinberg R . The hallmarks of cancer. Cell. 2000; 100(1):57-70. DOI: 10.1016/s0092-8674(00)81683-9. View

12.

Hermeking H . MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat Rev Cancer. 2012; 12(9):613-26. DOI: 10.1038/nrc3318. View

13.

Huh J, Kim T, Kim K, Song J, Jung Y, Jeong J . Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer. Br J Cancer. 2013; 109(2):452-61. PMC: 3721386. DOI: 10.1038/bjc.2013.305. View

14.

Iorio M, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S . MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65(16):7065-70. DOI: 10.1158/0008-5472.CAN-05-1783. View

15.

Iorio M, Casalini P, Tagliabue E, Menard S, Croce C . MicroRNA profiling as a tool to understand prognosis, therapy response and resistance in breast cancer. Eur J Cancer. 2008; 44(18):2753-9. DOI: 10.1016/j.ejca.2008.09.037. View

16.

Johnson S, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A . RAS is regulated by the let-7 microRNA family. Cell. 2005; 120(5):635-47. DOI: 10.1016/j.cell.2005.01.014. View

17.

Lagendijk M, Sadaatmand S, Koppert L, Tilanus-Linthorst M, de Weerd V, Ramirez-Moreno R . MicroRNA expression in pre-treatment plasma of patients with benign breast diseases and breast cancer. Oncotarget. 2018; 9(36):24335-24346. PMC: 5966243. DOI: 10.18632/oncotarget.25262. View

18.

Ma L, Teruya-Feldstein J, Weinberg R . Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007; 449(7163):682-8. DOI: 10.1038/nature06174. View

19.

Papadopoulos G, Alexiou P, Maragkakis M, Reczko M, Hatzigeorgiou A . DIANA-mirPath: Integrating human and mouse microRNAs in pathways. Bioinformatics. 2009; 25(15):1991-3. DOI: 10.1093/bioinformatics/btp299. View

20.

Paraskevopoulou M, Georgakilas G, Kostoulas N, Vlachos I, Vergoulis T, Reczko M . DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res. 2013; 41(Web Server issue):W169-73. PMC: 3692048. DOI: 10.1093/nar/gkt393. View