Despite significant advances in our understanding of the molecular and genetic intricacies of cancer, it remains one of the primary causes of death across the globe (Sung et al., 2021). Cancer cells complex heterogeneity and adaptive nature present significant challenges for developing effective therapeutic strategies (Goyal et al., 2023). Although there is increasing awareness of cancer, the primary focus is still on the DNA sequence that results in irregular protein synthesis. However, the use of next-generation sequencing (NGS) technology has led to the identification of many non-coding genes that are closely linked to the initiation and progression of tumors. Therefore, it is essential to understand how non-coding genes affect the tumorigenic process. Recent advances in sequencing technology have allowed for more complete genomic and transcriptome analysis, suggesting that up to 85% of the human genome is transcribed. This is unexpected given that only a small proportion of RNA transcripts in mammalian genomes encode protein products. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are longer than 200 nucleotides and do not code for proteins (Bhatti et al., 2021). They play a crucial role in regulating gene expression, cellular processes, and signaling pathways involved in cancer development and progression (Bhan et al., 2017, Schmitt and Chang, 2016). LncRNAs participate in various cellular activities, including modifying the structure of DNA, controlling gene activation, processing RNA after transcription, and regulating protein production (Kopp and Mendell, 2018). When lncRNAs are disrupted, it has been associated with different human diseases, including cancer, where they can act as either oncogenes, promoting tumor growth, or tumor suppressors, inhibiting tumor formation (Huarte, 2015, Wang and Chang, 2011). The discovery and characterisation of cancer-related lncRNAs have sparked interest in investigating their potential as biomarkers for diagnosis and prognosis and targets for therapeutic interventions (Huarte, 2015, Zhang et al., 2019). Finding effective strategies to manipulate lncRNA expression and function in cancer cells still poses a significant challenge.

The emergence of the CRISPR-Cas9 system, which stands for "Clustered Regularly Interspaced Short Palindromic Repeats" and the associated protein-9 nuclease, has brought about a revolutionary change in the realm of gene editing, offering a potent tool for manipulating genomic sequences (Jinek et al., 2012, Mali et al., 2013). Its widespread utilisation in cancer research has significantly contributed to identifying new targets for therapy, understanding cancer-causing mechanisms, and developing innovative cancer treatments (Sanchez-Rivera and Jacks, 2015). Importantly, CRISPR-Cas9 can be adapted to target and manipulate lncRNAs, opening up exciting possibilities for the advancement of lncRNA-based therapies for cancer (Lennox and Behlke, 2016, Yi and Li, 2016). In this article, e present a concise overview of lncRNAs, including their origin, molecular mechanisms, and involvement in the development and progression of cancer. We then delve into the details of the CRISPR-Cas9 system, its components, and its current applications in gene editing, gene therapy, and cancer research. Furthermore, we explore various strategies for manipulating lncRNA expression using CRISPR-Cas9, such as CRISPR interference (CRISPRi), CRISPR activation (CRISPRa), and CRISPR-Cas9-mediated knockout. We also address the existing challenges and limitations associated with targeting lncRNAs using CRISPR-Cas9, such as off-target effects, delivery methods, and regulatory complexities. Finally, we examine the potential therapeutic applications and clinical implications of CRISPR-Cas9-mediated lncRNA targeting in cancer treatment and offer an optimistic assessment of the future advancements in CRISPR-Cas9 technology, lncRNA research, and the convergence of these fields for the development of innovative cancer therapeutics.