Key Roles of Non-Coding RNAs in Breast Cancer Prognosis

Non-Coding RNAs: A Vital Component in Breast Cancer

Breast cancer continues to be a significant health crisis globally, with the World Health Organization reporting millions of new cases each year (WHO, 2020). The complexity of breast cancer biology requires the understanding of various molecular players involved in its progression, particularly non-coding RNAs (ncRNAs). Non-coding RNAs are categorized into two main classes: small ncRNAs (e.g., microRNAs) and long non-coding RNAs (lncRNAs). These molecules play pivotal roles in regulating gene expression, influencing fundamental cellular processes such as proliferation, apoptosis, and migration (Patel et al., 2024).

The significance of ncRNAs in breast cancer is underscored by their involvement in oncogenic pathways. For instance, certain lncRNAs, such as HOTAIR, NEAT1, and MALAT1, have been found to regulate critical genes associated with tumor growth and metastasis. MicroRNAs like miR-21 and miR-155 also have a profound impact on cancer progression by inhibiting tumor-suppressor genes or enhancing oncogenic signaling (Solaimani et al., 2025). Understanding the intricate roles of these ncRNAs can lead to innovative therapeutic strategies and serve as potential biomarkers for early cancer detection.

Long Non-Coding RNAs and Their Impact on Tumor Progression

Long non-coding RNAs (lncRNAs) have emerged as key regulators in breast cancer. They can modulate gene expression through various mechanisms, including chromatin remodeling, transcriptional regulation, and post-transcriptional modifications. One of the most extensively studied lncRNAs is HOTAIR, which has been shown to promote metastasis and drug resistance by regulating the epithelial-to-mesenchymal transition (EMT) and influencing various signaling pathways (Solaimani et al., 2025). Studies have demonstrated that overexpression of HOTAIR is associated with aggressive tumor characteristics and poor patient outcomes (Solaimani et al., 2025).

Another significant lncRNA is MALAT1, which plays a crucial role in cancer cell proliferation and invasion. Elevated levels of MALAT1 have been linked to advanced stages of breast cancer, and its inhibition has been shown to reduce tumor growth and enhance sensitivity to chemotherapy (Solaimani et al., 2025). NEAT1 also contributes to cancer progression by serving as a sponge for microRNAs, thus regulating pathways involved in cell migration and invasion (Solaimani et al., 2025).

Table 1: Key lncRNAs in Breast Cancer

MicroRNAs: Oncogenes and Tumor Suppressors in Breast Cancer

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally and are crucial in the development and progression of breast cancer. Many miRNAs act as oncogenes, promoting tumor growth, while others function as tumor suppressors. For instance, miR-21 is frequently upregulated in breast cancer and is associated with poor prognosis. It enhances proliferation and invasion by targeting tumor suppressor genes such as PTEN (Solaimani et al., 2025). Additionally, miR-155 is linked to increased aggressiveness, drug resistance, and metastasis in breast cancer (Solaimani et al., 2025).

Recent studies have highlighted the potential of miRNAs as biomarkers for breast cancer diagnosis and prognosis. The expression levels of certain miRNAs correlate with tumor stage and patient outcomes, making them valuable for therapeutic targeting (Solaimani et al., 2025).

Table 2: Key miRNAs in Breast Cancer

Mechanisms of Non-Coding RNAs in Cancer Drug Resistance

The role of non-coding RNAs in mediating drug resistance in breast cancer is a growing area of interest. Many cancer cells develop resistance to conventional therapies, leading to treatment failure. Non-coding RNAs, particularly miRNAs and lncRNAs, are implicated in several mechanisms of drug resistance, including alterations in drug metabolism, changes in apoptosis pathways, and modulation of cancer stem cell properties.

For example, lncRNA MALAT1 has been shown to enhance the resistance of breast cancer cells to doxorubicin by regulating the expression of genes involved in drug metabolism and apoptosis (Solaimani et al., 2025). Similarly, miR-21 promotes resistance by targeting apoptotic pathways and facilitating survival signaling in cancer cells (Solaimani et al., 2025).

Table 3: Mechanisms of Drug Resistance Mediated by Non-Coding RNAs

Potential of Non-Coding RNAs as Biomarkers in Cancer Therapy

The diagnostic and prognostic potential of non-coding RNAs in breast cancer is substantial. Their unique expression profiles in different cancer subtypes provide opportunities for non-invasive detection methods, such as liquid biopsies. The possibility of using ncRNAs as biomarkers for early detection of breast cancer is being explored, with various studies indicating that specific miRNAs and lncRNAs can serve as indicators of disease progression (Solaimani et al., 2025).

Moreover, the therapeutic application of ncRNAs is gaining traction. Strategies to inhibit oncogenic miRNAs or restore the expression of tumor suppressor miRNAs are under investigation. The ability to manipulate ncRNA levels presents a novel approach to enhance treatment efficacy and overcome drug resistance (Solaimani et al., 2025).

Table 4: Non-Coding RNAs as Potential Biomarkers

Conclusion

Non-coding RNAs are critical players in breast cancer biology, influencing tumor progression, metastasis, and drug resistance. Their diverse roles and unique expression patterns make them promising candidates for biomarkers and therapeutic targets. Continued research into the mechanisms underlying ncRNA function in breast cancer will be essential for developing innovative strategies for prevention, diagnosis, and treatment.

FAQ

What are non-coding RNAs?
Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins but play essential roles in regulating gene expression and cellular processes.

How do non-coding RNAs contribute to breast cancer?
Non-coding RNAs regulate tumor progression, metastasis, and drug resistance by interacting with various signaling pathways and gene expression networks.

Can non-coding RNAs be used as biomarkers?
Yes, specific non-coding RNAs have been identified as potential biomarkers for early diagnosis, prognosis, and treatment response in breast cancer.

What are some examples of non-coding RNAs in breast cancer?
Key examples include long non-coding RNAs like HOTAIR, MALAT1, and NEAT1, as well as microRNAs such as miR-21 and miR- What is the future of non-coding RNAs in cancer therapy?
The future includes developing strategies to target oncogenic non-coding RNAs or restoring tumor suppressor non-coding RNAs to improve treatment efficacy and overcome drug resistance.

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