Journal of Molecular Oncology Research

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
Reach Us +1 (202) 780-3397

Perspective - Journal of Molecular Oncology Research (2025) Volume 9, Issue 1

Exploring DNA damage response pathways and the role of long non-coding rnas in tumorigenesis

Mallory Taylor *

Department of Translational Oncology, University of São Paulo, Brazil

*Corresponding Author:
Mallory Taylor
Department of Translational Oncology, University of São Paulo, Brazil
E-mail: mallory@taylor.br

Received: 01-Jan-2025, Manuscript No. AAMOR -25-161678; Editor assigned: 02-Jan-2025, PreQC No. AAMOR -25-161678(PQ); Reviewed: 18-Jan-2025, QC No. AAMOR -25-161678; Revised: 22-Jan-2025, Manuscript No. AAMOR -25-161678(R); Published: 29-Jan-2025, DOI: 10.35841/ aamor-9.1.280

Citation: : Taylor M. Exploring DNA damage response pathways and the role of long non-coding rRNAs in tumorigenesis. J Mol Oncol Res. 2025;9(1):280.

Visit for more related articles at Journal of Molecular Oncology Research

Introduction

Cancer development is a complex process influenced by genetic and epigenetic alterations. Among these, the DNA damage response (DDR) pathways play a crucial role in maintaining genomic stability and preventing tumorigenesis. When DDR mechanisms fail, cells accumulate mutations that contribute to cancer progression. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of DDR pathways, influencing cellular responses to DNA damage and affecting cancer cell behavior. Understanding the interplay between DDR pathways and lncRNAs could open new avenues for cancer therapy and biomarker discovery [1].

DDR pathways are essential mechanisms that detect and repair DNA damage caused by environmental stressors, radiation, and metabolic processes. These pathways include base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and non-homologous end joining. The activation of DDR pathways prevents genetic instability, which is a hallmark of cancer. Mutations in key DDR genes, such as TP53, ATM, and BRCA1/2, often lead to impaired DNA repair, increasing susceptibility to tumorigenesis [2].

LncRNAs are a class of RNA molecules longer than 200 nucleotides that do not code for proteins but regulate gene expression at various levels, including chromatin modification, transcription, and post-transcriptional processes. Increasing evidence suggests that lncRNAs are involved in modulating DDR pathways, thereby influencing cancer development and progression. Their regulatory functions in DNA repair mechanisms make them potential therapeutic targets [3].

Several lncRNAs have been identified as key players in DNA damage sensing. For example, NORAD (Non-Coding RNA Activated by DNA Damage) is known to maintain genome stability by interacting with RNA-binding proteins. In contrast, other lncRNAs, such as DDSR1, modulate the activation of DDR pathways by interacting with repair proteins. The dysregulation of these lncRNAs can lead to improper DNA damage responses, contributing to tumorigenesis [4].

Homologous recombination (HR) is a high-fidelity DNA repair mechanism crucial for fixing double-strand breaks. LncRNAs such as LINP1 have been shown to enhance HR efficiency, promoting DNA repair in cancer cells. In contrast, certain lncRNAs can suppress HR, leading to increased genomic instability and cancer progression. Targeting these regulatory lncRNAs could be a promising strategy for sensitizing tumors to DNA-damaging therapies [5].

Non-homologous end joining (NHEJ) is an error-prone repair mechanism that can lead to mutations if not properly regulated. LncRNAs like MALAT1 have been found to influence NHEJ by recruiting repair proteins to DNA break sites. The upregulation of such lncRNAs in cancer cells often leads to increased survival despite accumulating mutations, highlighting their role in tumorigenesis [6].

Given their regulatory roles in DDR pathways, lncRNAs present potential therapeutic targets for cancer treatment. Strategies such as RNA interference (RNAi) and antisense oligonucleotides can be used to modulate lncRNA expression, thereby enhancing the efficacy of DNA-damaging agents like chemotherapy and radiation therapy. Additionally, lncRNA-based biomarkers could be developed for early cancer detection and prognosis [7, 8].

While the therapeutic targeting of lncRNAs is promising, challenges remain in understanding their precise mechanisms and interactions. The specificity of lncRNA functions in different cancer types necessitates further research to identify context-dependent effects. Advances in CRISPR-based gene editing and RNA-targeted therapies could help overcome these challenges and pave the way for personalized cancer treatment strategies [9, 10].

Conclusion       

The intricate relationship between DDR pathways and lncRNAs highlights the complexity of tumorigenesis. As key regulators of DNA repair mechanisms, lncRNAs offer new insights into cancer progression and potential therapeutic interventions. Future research should focus on unraveling the specific molecular mechanisms by which lncRNAs influence DDR pathways, ultimately leading to improved cancer treatment strategies. Understanding and targeting these non-coding RNAs could revolutionize cancer therapy and enhance patient outcomes.

References

  1. Alves-Bezerra M, Cohen DE. Triglyceride metabolism in the liver.Compr Physiol. 2017;8(1):1.

    2. Indexed at, Google Scholar, Cross Ref

  2. Arslan N. Obesity, fatty liver disease and intestinal microbiota.World J Gastroenterol. 2014;20(44):16452.

    3. Indexed at, Google Scholar, Cross Ref

  3. Church C, Horowitz M, Rodeheffer M. WAT is a functional adipocyte?. 2012;1(1):38-45.

    4. Indexed at, Google Scholar, Cross Ref

  4. Di Mauro S, Trevisan C, Hays A. Disorders of lipid metabolism in muscle.Muscle Nerve Off J Am Assoc Electrodiagn Med. 1980;3(5):369-88.

    5. Indexed at, Google Scholar, Cross Ref

  5. Fahy E, Subramaniam S, Brown HA, et al. A comprehensive classification system for lipids.J Lipid Res. 2005;46(5):839-61.

    6. Indexed at, Google Scholar, Cross Ref

  6. Simopoulos AP. Nutrigenetics/nutrigenomics.Ann Rev Public Health. 2010;31:53-68.

    7. Indexed at, Google Scholar, Cross Ref

  7. Corella D, Ordovas JM. Nutrigenomics in cardiovascular medicine.Circ Cardiovasc Genet. 2009;2(6):637-51.

    8. Indexed at, Google Scholar, Cross Ref

  8. Trujillo E, Davis C, Milner J. Nutrigenomics, proteomics, metabolomics, and the practice of dietetics.J Am Diet Assoc. 2006 Mar 1;106(3):403-413.

    9. Indexed at, Google Scholar, Cross Ref

  9. Ferguson LR. Nutrigenomics approaches to functional foods.J Am Diet Assoc. 2009;109(3):452-8.

    10. Indexed at, Google Scholar, Cross Ref

  10. Kaput J. Nutrigenomics research for personalized nutrition and medicine.Curr Opin Biotechnol. 2008;19(2):110-20.

    11. Indexed at, Google Scholar, Cross Ref

Get the App