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MicroRNA-99a-5p suppresses breast cancer progression and cell-cycle pathway through downregulating CDC25A

Hongzhen Qin1, Wenfei Liu1

  • 1Department of General Surgery, 305 Hospital of PLA, Beijing, China.

Journal of Cellular Physiology
|November 17, 2018
PubMed

Insights

MicroRNA-99a-5p targets CDC25A, suppressing its expression in breast cancer. This microRNA (miRNA) inhibits cancer cell proliferation and invasion while promoting apoptosis, offering a potential therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Breast cancer is a significant global health concern with complex molecular underpinnings.
  • Dysregulation of microRNAs (miRNAs) and their target genes plays a critical role in cancer development and progression.
  • Understanding the specific roles of miRNAs like miR-99a-5p in breast cancer is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the association between miR-99a-5p and CDC25A in breast cancer.
  • To elucidate the regulatory mechanisms of miR-99a-5p on breast cancer progression.
  • To evaluate the therapeutic potential of modulating miR-99a-5p in breast cancer.

Main Methods:

  • Analysis of gene and miRNA expression using The Cancer Genome Atlas (TCGA) microarray data.
  • Quantitative real-time polymerase chain reaction (qRT-PCR) to measure miR-99a-5p and CDC25A levels.
  • Western blot analysis for protein expression (CDC25A, ki67, cyclin D1, p21, BAX, BCL-2, BCL-XL, MMP2, MMP9).
  • Bioinformatics analysis and dual luciferase assay to confirm the targeting relationship.
  • In vitro assays (cell counting kit-8, Transwell, flow cytometry) to assess cell proliferation, invasion, and apoptosis.
  • In vivo studies using a nude mouse xenograft model.

Main Results:

  • miR-99a-5p was significantly downregulated, while CDC25A was upregulated in breast cancer tissues and cells.
  • miR-99a-5p directly targets and suppresses CDC25A expression in breast cancer cells.
  • Overexpression of miR-99a-5p inhibited cell proliferation and invasion, and promoted apoptosis.
  • miR-99a-5p overexpression repressed CDC25A, ki67, and Cyclin D1, while upregulating p21.
  • Downregulation of miR-99a-5p and upregulation of CDC25A activated cell-cycle progression.

Conclusions:

  • miR-99a-5p acts as a tumor suppressor in breast cancer by targeting CDC25A.
  • Modulating miR-99a-5p expression can inhibit breast cancer cell proliferation, invasion, and affect apoptosis.
  • The miR-99a-5p/CDC25A axis is a critical regulator of breast cancer cell-cycle progression and represents a potential therapeutic target.
Keywords:
CDC25Abreast cancercell-cycle pathwaymiR-99a-5p

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