Silent Sentinels of Tumor Biology: Unveiling the Protective and Regulatory Roles of Small Non-Coding RNAs in Gallbladder Cancer and the Promise of Gene Editing

Gallbladder cancer develops in the epithelial cells lining the gallbladder and is associated with risk factors such as chronic inflammation, gallstones, and certain genetic predispositions. Although relatively rare, it presents significant treatment challenges, with approximately ۱۹۸,۰۰۰ new cases diagnosed globally in ۲۰۲۰ and around ۶۶,۰۰۰ deaths. Often detected at advanced stages, this cancer has a poor prognosis, with an average survival of about ۱۲ months and a five-year survival rate of only ۵ to ۱۵ percent. A promising advancement in treating gallbladder cancer is gene editing, which allows for the precise modification of DNA sequences within living organisms' genomes. This technology enables scientists to delete, add, or alter genes, enhancing disease treatment and research. Among the most advanced techniques is CRISPR/Cas۹, a groundbreaking tool that targets cancer cells directly. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) functions as a natural immune defense in bacteria, with Cas۹ acting as "enzyme scissors" to cleave DNA strands. By designing a guide RNA (gRNA) that binds to a specific DNA sequence, Cas۹ can be directed precisely to the targeted site within the genome. Methods: This study examined articles published in English from ۲۰۱۶ to ۲۰۲۴, sourced from Scopus, PubMed, and Web of Science, focusing on the impact of small non-coding RNAs. Using relevant keywords, such as CRISPR/Cas۹, chemotherapy responsiveness, small non-coding RNAs, brain cancer, and gene regulation, articles were selected based on specific exclusion criteria and included in the final analysis after a comprehensive review. Results: Our investigation into review articles has led us to several key conclusions regarding the use of CRISPR/Cas۹ in the treatment of gallbladder cancer. Our findings suggest that specific genes implicated in the development of this cancer can be effectively targeted using CRISPR/Cas۹. This innovative technique not only mitigates the effects of tumor-associated proteins but also enhances the overall efficacy of treatments. Furthermore, gene editing could improve the sensitivity of gallbladder cancer cells to chemotherapy by altering the expression of genes associated with drug resistance. Moreover, the integration of gene editing techniques with small non-coding RNAs has shown significant promise in amplifying their regulatory effects. Small non-coding RNAs, including miRNA (MicroRNA) and siRNA (Small Interfering RNA), play vital roles in gene expression regulation. miRNA modulates gene expression by binding to messenger RNA (mRNA), either inhibiting translation or promoting degradation; fluctuations in miRNA levels can profoundly affect gallbladder cancer progression. Meanwhile, siRNA facilitates gene silencing by binding to specific mRNAs, leading to their degradation, which may serve as an effective therapeutic strategy for gallbladder cancer. This comprehensive analysis highlights the transformative potential of CRISPR/Cas۹ and small non-coding RNAs in combating gallbladder cancer, underscoring the necessity for ongoing research and clinical application to enhance patient outcomes. Conclusion: Gene editing methods, especially CRISPR/Cas۹, hold significant promise for advancing the treatment of gallbladder cancer. These approaches can serve as innovative therapeutic strategies to manage this cancer type and improve treatment outcomes. However, further research and clinical trials are necessary to confirm the safety and effectiveness of these methods.

کلیدواژه ها:

CRISPR/Cas۹ ، Chemotherapy Sensitivity ، MicroRNAs (miRNAs) ، Gallbladder Cancer ، Gene Expression