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Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
The Potential of Noncoding RNAs-siRNAs in Cancer Research and Therapy: Challenges and Solutions
Himanshu1, Mudasir Bashir2, Moien Lone3
1Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Abstract:
Noncoding RNAs (ncRNAs) are RNA molecules, which play critical roles in regulating gene expression and cellular activities, influencing processes like differentiation, proliferation, and cell survival, unlike messenger RNAs (mRNAs) that act as templates for protein production. Examples of ncRNAs include small interfering RNAs (siRNAs), microRNAs (miRNAs), ribosomal RNAs, transfer RNAs, small nucleolar RNAs (sno RNAs), and small nuclear RNAs (snRNAs). Small interfering RNAs (siRNAs) are a type of noncoding RNA that function primarily by silencing specific genes through a process called RNA interference (RNAi), in which they bind to complementary messenger RNA (mRNA) molecules, causing their degradation and preventing the translation of that mRNA into protein; essentially, they act as a "gene silencing" mechanism by targeting and destroying specific transcripts. In this chapter, we review the biogenesis, functions, and role of RNAs (siRNAs), in cancer research and role in therapy. siRNA (small interfering RNA) denotes small interfering RNA, consisting of 21-25 nucleotides. Discovery of siRNA (small interfering RNA) has been a significant breakthrough in biology. Small interfering RNAs (siRNAs) are single-stranded RNAs that are formed by the cleavage of longer double-stranded RNAs by the enzyme DICER1 within the RISC loading complex, which includes DICER1, an Argonaute protein, and either TARBP2 or PRKRA (PACT). Small interfering RNA (siRNA) is essential for health as it serves as a natural gene silencing tool, controlling gene expression posttranscriptionally, and is involved in several cellular processes such as development, immune response, and stress response; however, when not regulated properly, siRNAs may lead to diseases like cancer and viral infections, positioning them as a promising therapeutic target for targeted gene silencing therapies. siRNAs play a pivotal role in RNA interference (RNAi), a natural cellular process where they degrade complementary mRNA targets, preventing protein synthesis. This gene silencing mechanism has proven to be a valuable tool for controlling gene expression in research and therapeutic contexts. In cancer, siRNAs offer a promising approach to selectively silence oncogenes or other genes involved in tumor progression, thus hindering the development and spread of malignancies. However, the therapeutic potential of siRNAs faces several challenges, including efficient delivery to target cells, off-target effects, and stability issues. This chapter focuses on the biogenesis and functional significance of siRNAs, exploring their roles in cancer research and their promising therapeutic potential. With the continued advancement of RNA-based technologies, siRNAs hold considerable promise as a powerful tool for cancer treatment, offering new avenues for targeted therapies and personalized medicine.
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