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Bioinformatics identification of dysregulated microRNAs in triple negative breast cancer based on microRNA expression

Junqing Chen1, Zhanhong Chen1, Jian Huang1

  • 1Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.

Oncology Letters
|February 14, 2018
PubMed

Insights

Triple negative breast cancer (TNBC) is aggressive, but microRNAs (miRNAs) offer new therapeutic targets. This study identified 107 differentially expressed miRNAs in TNBC cells, highlighting potential biomarkers and treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple negative breast cancer (TNBC) represents 15-20% of breast cancers and is associated with aggressive behavior and poor prognosis.
  • MicroRNAs (miRNAs) are increasingly recognized for their roles in cancer development and progression, presenting potential therapeutic avenues for TNBC.
  • Identifying specific miRNA dysregulations in TNBC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate and characterize the differential miRNA expression profiles in TNBC cells compared to non-TNBC cells.
  • To identify key miRNAs and their associated signaling pathways involved in TNBC progression and metastasis.
  • To explore the potential of dysregulated miRNAs as diagnostic biomarkers and therapeutic targets for TNBC.

Main Methods:

  • MicroRNA microarray analysis was performed to compare miRNA expression between MDA-MB-231 (TNBC) and MCF-7 (non-TNBC) cell lines.
  • Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression levels of selected dysregulated miRNAs.
  • Gene ontology and pathway enrichment analyses were conducted to identify the biological functions and signaling pathways associated with the identified miRNAs and their predicted targets.

Main Results:

  • A total of 107 differentially expressed miRNAs were identified, with 57 upregulated and 50 downregulated in MDA-MB-231 cells compared to MCF-7 cells.
  • Five miRNAs (miR-200c-3p, miR-221-3p, miR-222-3p, miR-192-5p, and miR-146a) were confirmed to be significantly dysregulated.
  • The dysregulated miRNAs and their targets were found to be enriched in critical signaling pathways such as MAPK, Wnt, and TGF-β, which are implicated in TNBC progression and metastasis.
  • Network analysis suggested miR-200c as a potentially crucial miRNA in breast cancer.

Conclusions:

  • Aberrant miRNA expression plays a significant role in the pathogenesis of triple negative breast cancer.
  • Dysregulated miRNAs, particularly miR-200c, represent promising candidates for novel biomarkers and therapeutic targets in TNBC.
  • Understanding miRNA involvement in key signaling pathways provides insights into TNBC progression and potential treatment strategies.
Keywords:
bioinformaticsbiomarkermiRNAtherapeutic targettriple negative breast cancer

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