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INTERNATIONAL CONGRESS OF

CancerGenetics

• A Review of the Regulatory Role of Long Non-Coding RNA GAS5 in Breast Cancer

• Iliya Ahmadzadeh kermani,¹ Elahe Kamelnia,^2,* Reyhane Kamelnia,³ Seyed Ali Mojtabavi,⁴
  1. Department of biology, Faculty of sciences, Mashhad branch, Islamic Azad University, Mashhad, Iran
  2. Department of biology, Faculty of sciences, Mashhad branch, Islamic Azad University, Mashhad, Iran
  3. Faculty of Medicine, Mashhad University of Azad Medical Sciences, Mashhad, Iran
  4. Department of biology, Faculty of sciences, Mashhad branch, Islamic Azad University, Mashhad, Iran
  
  
  
• Introduction: Breast cancer (BC) is the most common malignancy among women worldwide. This disease results from various factors such as exposure to endogenous and exogenous estrogens, lifestyle choices, excessive consumption of food and alcohol, obesity, and toxic environmental agents including pollutants, heavy metals, and chemicals. Approximately 15% of breast cancers are linked to genetic predisposition and hereditary factors. Among women, cancer is the second leading cause of death, with nearly 7 million new cases and 3.5 million deaths reported annually. Breast cancer is the most prevalent cancer in women, accounting for about 30% of all female cancer cases and causing approximately 500,000 deaths per year. Long non-coding RNAs (lncRNAs) are a class of RNA molecules longer than 200 nucleotides that do not code for proteins. These lncRNAs play crucial roles in either suppressing or promoting tumor growth by regulating various functions and mechanisms in cancer cells, including proliferation, invasion, metastasis, apoptosis, and resistance to different therapeutic approaches. GAS5 belongs to the 5'-terminal oligopyrimidine (5'-TOP) gene family, which includes genes encoding all ribosomal proteins, elongation factors involved in protein synthesis, and many others. Studies on the molecular mechanisms underlying the dysregulation of GAS5, such as DNA hypermethylation of the CpG island in the gene's promoter region, have been discussed. GAS5 is capable of sequestering microRNAs and modulating the expression levels of their mRNA targets, particularly those involved in cellular invasion and apoptosis.
• Methods: Reduced expression of the growth arrest-specific long non-coding RNA (GAS5) transcript has been observed in various tumors, indicating its role as a tumor suppressor. GAS5 interacts with proteins, DNA, and microRNAs (miRNAs), leading to increased expression of several mRNAs encoding tumor suppressors like PTEN. This increased expression inhibits tumor growth. GAS5 promotes apoptosis by regulating apoptotic proteins such as caspases and members of the BCL2 family. Conversely, low levels of GAS5 enhance tumor invasion, metastasis, and overall aggressiveness. GAS5 also influences tumor cell proliferation by regulating signaling pathways. Its role in modulating apoptosis and tumor aggressiveness in breast cancer highlights its potential as a therapeutic target. Aggressive tumors often exhibit rapid growth, genetic instability, and resistance to apoptosis, which limit treatment options.
• Results: Furthermore, GAS5 can interact with various miRNAs and thereby attenuate their effects on mRNA targets. GAS5 acts as a competing endogenous RNA (ceRNA) for several oncogenic miRNAs, including miR-21-5p, miR-221-3p, miR-196a-5p, miR-378-5p, as well as the tumor suppressor miR-216b. miR-21-5p, the most commonly upregulated miRNA in malignancies, exerts its function by regulating tumor suppressor genes such as PTEN, TPM1, and PDCD4. The interaction between GAS5 and miR-21-5p has been confirmed by RNA immunoprecipitation and RNA pulldown assays, demonstrating reciprocal regulation in breast cancer cells. In addition, GAS5 functions as a ceRNA for miR-196a-5p in breast cancer cells, and may also interact with miR-216b.
• Conclusion: In conclusion, considering the critical role of long non-coding RNAs like GAS5 in breast cancer, decreased GAS5 expression leads to increased invasion, metastasis, and resistance to treatment, underscoring its function as an effective tumor suppressor. The complex interactions between GAS5 and miRNAs reveal important regulatory mechanisms controlling cancer cell growth. These findings highlight the potential of targeting GAS5 as a novel therapeutic approach in breast cancer treatment.
• Keywords: Breast cancer _ Long non coading Gas5 _ Long non-coding RNA