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LncRNAs at the Crossroads of Breast Cancer Metastasis: Emerging Mechanisms and Therapeutic Prospects
Arnab Dey1, Kuppa Sree Vagdevi1, Mohini Singh1
1Department of Life Science, Sharda School of Bioscience and Technology, Sharda University, Greater Noida, India.
Abstract:
Breast cancer metastasis is one of the leading causes of cancer-related mortality in women, which occurs through an intricate molecular network and cellular events. Over time, lncRNAs have emerged as an important regulator of metastatic progression. These RNAs affect important processes including EMT, ECM remodelling, angiogenesis, immune evasion, and can-cer stemness. LncRNAs regulate this process by acting as molecular decoys, scaffolds, guides, or competing endogenous RNAs, thereby controlling gene expression at both transcriptional and post-transcriptional levels. Various lncRNAs, including HOTAIR, BCAR4, and LINC00511, are known to promote metastasis by driving chromatin remodelling and activating pro-tumorigenic signalling pathways. In contrast, lncRNAs such as GAS5, LINC01133, and TINCR act as metas-tasis suppressors, thereby limiting tumor spreading. A wide range of experimental approaches, including CRISPR/Cas9, RNA interference, in-vitro functional assays, in-vivo models, and bio-informatic analyses, have helped define critical lncRNA-driven regulatory networks. Despite these advances, challenges related to lncRNA conservation, delivery strategies, and context-spe-cific functions persist. Nevertheless, progress in RNA therapeutics and multi-omics technologies is steadily advancing the integration of lncRNA signatures into liquid biopsies, diagnostics, and precision medicine approaches for metastatic breast cancer.
Insights
Long non-coding RNAs (lncRNAs) are key regulators of breast cancer metastasis, acting as either promoters or suppressors. Understanding lncRNA networks is crucial for developing new diagnostics and therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer metastasis is a major cause of cancer mortality.
- Long non-coding RNAs (lncRNAs) play critical roles in regulating metastatic processes.
- lncRNAs influence key events like epithelial-mesenchymal transition (EMT), angiogenesis, and cancer stemness.
Purpose of the Study:
- To review the multifaceted roles of lncRNAs in breast cancer metastasis.
- To highlight lncRNAs that promote or suppress metastasis.
- To discuss experimental approaches and challenges in lncRNA research for metastatic breast cancer.
Main Methods:
- Literature review of lncRNA functions in breast cancer metastasis.
- Analysis of experimental approaches including CRISPR/Cas9, RNA interference, in-vitro/in-vivo models, and bioinformatics.
- Examination of lncRNA regulatory mechanisms (decoys, scaffolds, guides, ceRNAs).
Main Results:
- Specific lncRNAs (e.g., HOTAIR, BCAR4) promote metastasis by altering chromatin and signaling pathways.
- Other lncRNAs (e.g., GAS5, LINC01133) act as metastasis suppressors.
- lncRNAs regulate gene expression at transcriptional and post-transcriptional levels.
Conclusions:
- lncRNAs are pivotal in breast cancer metastasis, with context-specific functions.
- Challenges in lncRNA research include conservation, delivery, and functional specificity.
- Advances in RNA therapeutics and multi-omics pave the way for lncRNA integration into diagnostics and precision medicine for metastatic breast cancer.
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