en Genetics Genetics مقاله مروری Review Article <div style="text-align: justify;"><span style="line-height:2;"><span style="font-size:14px;"><span style="font-family:Times New Roman;"><strong>Introduction:</strong> Cancer pathogenesis is characterized by the acquisition of hallmark capabilities that collectively enable tumor initiation, progression, and metastatic dissemination. Among the diverse regulatory elements implicated in these processes, long non-coding RNAs (lncRNAs) have emerged as pivotal modulators of cancer biology. Through multilayered regulation of gene expression, chromatin remodeling, epigenetic modification, and signal transduction pathways, lncRNAs orchestrate key oncogenic and tumor-suppressive networks. &nbsp;Accumulating evidence implicates representative lncRNAs, including MALAT1, MEG3, GAS5, HOTAIR, TERRA, XIST, and UCA1, in the context-dependent regulation of proliferation, cell-death responses, telomere maintenance, angiogenesis, and invasion and metastasis.<br> <strong>Aim:</strong> This narrative review aims to critically synthesize current evidence regarding the mechanistic roles of key lncRNAs across established cancer hallmarks and to delineate their contributions to oncogenic and tumor-suppressive regulatory circuits. &nbsp;Furthermore, the review examines artificial intelligence (AI)-based approaches to lncRNA identification, functional annotation, and disease-association prediction, with attention to their evaluated tasks, limitations, and requirements for biological validation.<br> <strong>Conclusion: </strong>&nbsp;Current studies implicate lncRNAs in several cancer-associated processes through transcriptional, post-transcriptional, and chromatin-related regulation. Their context-dependent effects support further investigation as candidate biomarkers and therapeutic targets. However, experimental findings, patient associations, and clinical validation represent different types of evidence. AI methods can assist computational annotation and candidate prioritization, while molecular mechanisms and clinical usefulness require independent confirmation.</span></span></span></div> Cancer, Long Non-Coding RNAs, Hallmarks of Cancer, Biomarkers, Targeted Therapy, Artificial Intelligence. 77 89 http://ijbc.ir/browse.php?a_code=A-10-2412-2&slc_lang=en&sid=1 Pejman Hosseinzadeh No Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Elaheh Gheyb No Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Mehdi Rostami No Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak,Iran. Ghazaleh Doostparast No Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. Saeedeh Askarian No Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. Sobhan Pouramini No Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran. Mehraneh Nouri No Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Mohammad Soukhtanloo soukhtanloom@gmail.com No Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Ramin Raoufinia r.raoofi69@gmail.com Yes Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.