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LncRNA TMPO-AS1 Promotes Triple-Negative Breast Cancer by Sponging miR-383-5p to Trigger the LDHA Axis

  • 0Department of Bioscience, Manipal University Jaipur, University Jaipur, Dehmi Kalan, Jaipur-Ajmer Expressway, Jaipur, Rajasthan, 303007, India.
Asian Pacific Journal of Cancer Prevention : Apjcp +

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August 29, 2024

|

August 29, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Lactate dehydrogenase A (LDHA) overexpression in breast cancer correlates with poor survival and metastasis. Natural compounds like Withaferine A show potential as LDHA inhibitors for targeted therapy.

Area Of Science

  • Oncology
  • Molecular Biology
  • Biochemistry

Background

  • Breast cancer heterogeneity necessitates understanding molecular drivers like Lactate Dehydrogenase A (LDHA) expression.
  • The role of non-coding RNAs in regulating LDHA and their prognostic significance in breast cancer remains largely unexplored.

Purpose Of The Study

  • To investigate the prognostic implications of LDHA expression in breast cancer.
  • To explore the regulatory network of LDHA, including non-coding RNAs and their association with tumor-infiltrating immune cells.
  • To identify potential therapeutic agents targeting LDHA.

Main Methods

  • Bioinformatic analysis of gene expression and survival data from public repositories (TIMER 2.0, UALCAN, TISIDB, Breast Cancer Gene Expression Miner).
  • Exploration of the relationship between LDHA, non-coding RNAs (e.g., TMPO-AS1, miR-383-5p), and tumor-infiltrating immune cells using GSCA and TISIDB.
  • Molecular docking simulations using Auto Dock Tools to assess the binding affinity of withanolides and an inhibitor (LDH-IN-1) with LDHA.

Main Results

  • LDHA overexpression is linked to reduced recurrence-free survival, overall survival, and distant metastasis-free survival in breast cancer patients.
  • Invasive breast cancer exhibits overexpression of LDHA, HIF-1α, and TMPO-AS1, alongside downregulation of miR-383-5p, correlating with poor prognosis.
  • Withanolides (Withaferine A, Withanolide D) demonstrated high binding affinity to LDHA, suggesting potential as small-molecule inhibitors.

Conclusions

  • LDHA overexpression serves as a negative prognostic biomarker in breast cancer.
  • The LDHA/HIF-1α/TMPO-AS1 axis and miR-383-5p dysregulation are implicated in breast cancer progression and immune microenvironment modulation.
  • Withanolides represent promising candidates for developing novel LDHA-targeted therapies for breast cancer.

Keywords:

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