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Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 3657

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Special Issue Editor

Dr. Bodhisattwa Banerjee

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Guest Editor

Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT, USA
Interests: long non-coding RNAs; molecular mechanisms; gene regulation; disease implications; therapeutic potential

Special Issue Information

Dear Colleagues,

This Special Issue concentrates on the expanding field of long non-coding RNAs (lncRNAs) and their pivotal contributions to disease pathophysiology. While lncRNAs were once viewed merely as transcriptional noise, recent findings indicate they participate in diverse cellular functions, including gene regulation, chromatin remodeling, and RNA splicing. By integrating current research and advanced methodologies, this collection of articles aims to highlight how lncRNAs modulate molecular processes in cancer, neurodegenerative disorders, cardiovascular diseases, and more. The presented studies emphasize both basic and translational research, revealing how targeting or harnessing lncRNAs might shape new therapeutic strategies. Contributors discuss emerging technologies for lncRNA profiling, functional characterization, and validation, offering a roadmap for identifying disease-specific biomarkers and tailoring targeted interventions. Overall, this Special Issue seeks to stimulate discussion on the dynamic roles of lncRNAs, catalyzing future investigations and advancing the development of innovative treatments for diverse human diseases. These advances aim to foster meaningful clinical breakthroughs.

Dr. Bodhisattwa Banerjee
Guest Editor

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Keywords

long non-coding RNAs (lncRNAs)
gene regulation
molecular mechanisms
chromatin remodeling
epigenetic control
disease pathophysiology
biomarker discovery
therapeutic strategies
translational research

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Published Papers (4 papers)

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Research

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23 pages, 4305 KB

Open AccessArticle

Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation

by Adrian Albulescu, Alina Fudulu, Mirela Antonela Mihaila, Iulia Iancu, Adriana Plesa, Marinela Bostan, Anca Botezatu, Lorelei Irina Brasoveanu and Camelia Mia Hotnog

Curr. Issues Mol. Biol. 2025, 47(10), 863; https://doi.org/10.3390/cimb47100863 - 18 Oct 2025

Viewed by 659

Abstract

Thyroid carcinomas are phenotypically heterogeneous malignancies. Advances in molecular and cellular technologies have revealed genetic, epigenetic, and nongenetic factors underlying this heterogeneity. Our study aimed to assess the impact of single and combined treatments with anticancer agents (Carboplatin, Doxorubicin, Paclitaxel, Avastin), natural compounds (Quercetin), and epigenetic modulators (suberoylanilide hydroxamic acid and 5-Azacytidine) on the expression of long noncoding RNAs, methylation regulators, and functional features in the human thyroid cancer cell line K1. Methods: Treated and untreated K1 cells were used throughout experiments to evaluate the drug-induced cytotoxicity, apoptosis, cell cycle distribution, cytokine release, gene expression, and global DNA methylation levels. Results: Some single- and combined-drug treatments modulated both cell cycle progression and apoptotic events, demonstrating anti-tumor activity of the tested compounds. Gene expression analysis showed treatment-specific regulation of target genes and lncRNAs, including both upregulation and downregulation across different drug combinations. All treatments resulted in increased global DNA methylation levels compared to the untreated controls. Several combinations significantly upregulated DNMT1 and DNMT3B, while concomitantly decreased EZH2 levels. Conclusions: These coordinated epigenetic changes highlight the therapeutic potential of combining epigenetic modulators with chemotherapeutic agents, suggesting a strategy to prevent or reverse treatment resistance and improve outcomes in thyroid cancer patients. Full article

(This article belongs to the Special Issue Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy)

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18 pages, 1105 KB

Open AccessArticle

lncRNAs as Biomarkers of Hepatocellular Carcinoma Risk and Liver Damage in Advanced Chronic Hepatitis C

by Driéle B. dos Santos, Geysson J. Fernandez, Letícia T. Silva, Giovanni F. Silva, Estela O. Lima, Aline F. Galvani, Guilherme L. Pereira and Adriana C. Ferrasi

Curr. Issues Mol. Biol. 2025, 47(5), 348; https://doi.org/10.3390/cimb47050348 - 10 May 2025

Cited by 1 | Viewed by 1583

Abstract

Background/Objectives: LncRNAs have emerged as promising biomarkers due to their role in gene regulation of carcinogenesis and presence in biological fluids. Liquid biopsies offer a less invasive alternative to tissue biopsies, improving early cancer diagnosis and surveillance. Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers. Late diagnoses contribute to poor prognosis, particularly in chronic hepatitis C (CHC) patients, which is a major risk factor for HCC. Tissue biopsies for HCC diagnosis pose risks, including tumor dissemination, highlighting the urgent need for noninvasive biomarkers. Several lncRNAs are deregulated in HCC and may be potential markers for assessing HCC risk in CHC. This study evaluated seven lncRNAs as plasma biomarkers for HCC risk in CHC. Methods: lncRNA expression was analyzed by RT-qPCR in three groups: CHC patients who developed HCC within a 5-year follow-up (HCCpos), CHC patients who did not develop HCC within a 5-year follow-up (HCCneg), and healthy blood donors (CG). Results: This study found that plasma lncRNAs HULC and RP11-731F5.2 are potential biomarkers for HCC risk, while RP11-731F5.2 and KCNQ1OT1 may serve as noninvasive biomarkers for liver damage due to HCV infection. Conclusions: These findings highlight the potential of lncRNAs in enhancing early diagnosis and monitoring of HCC in CHC patients. Full article

(This article belongs to the Special Issue Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy)

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Review

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15 pages, 1048 KB

Open AccessReview

miRNAs and Alcohol-Related Hepatitis

by Dinuka Bandara, Clara Ashraf Boshra Shaker Romany, Vikash Kumar, Aalam Sohal, Mohanad Al-Qaisi and Nilofar Najafian

Curr. Issues Mol. Biol. 2025, 47(12), 1048; https://doi.org/10.3390/cimb47121048 - 15 Dec 2025

Abstract

Alcohol-related hepatitis (AH) is a severe, life-threatening liver inflammation caused by chronic heavy drinking, with high short-term mortality despite abstinence and supportive care. The pathophysiology involves a compromised gut–liver axis, activation of Kupffer cells, stimulation of hepatic stellate cells, and progressive fibrosis. Increasing evidence suggests that microRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, play a role as modulators of these processes. Understanding dysregulated miRNAs in AH may provide insights into novel diagnostic and therapeutic interventions. Several miRNAs have been identified as critical regulators of AH pathogenesis. Upregulated miRNAs, including miRNA-217, miRNA-182, let-7b, miRNA-21, and miRNA-34a, promote inflammation through NF-κB activation, Toll-like receptor (TLR) signaling, cytokine production, and ductular reactions. Conversely, downregulated miRNAs such as miRNA-148a, miRNA-30e, and miRNA-483-3p are associated with impaired hepatocyte differentiation, dysregulated oxidative stress responses, and enhanced Mallory–Denk body formation. Considering that miRNAs are pivotal regulators of AH pathophysiology including immune activation, hepatocyte death, fibrosis, and metabolic dysregulation, their altered expression patterns not only illuminate key pathogenic pathways but also provide promising avenues for biomarker discovery and therapeutic targeting. This review aims to summarize the current literature regarding the miRNA profiles involved in alcohol-related hepatitis, their individual mechanistic roles in pathogenesis of AH, and their potential for biomarkers. Full article

(This article belongs to the Special Issue Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy)

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22 pages, 787 KB

Open AccessReview

Long Non-Coding RNAs: Significant Drivers of Carcinogenesis Mechanisms in Head and Neck Squamous Cell Carcinoma

by Camelia Mia Hotnog, Marinela Bostan, Matei Anghelescu, Viviana Roman, Coralia Bleotu, Razvan Hainarosie, Catalina Voiosu, Stefania Marineata, Ioana-Stefania Bostan, Carmen Cristina Diaconu and Mirela Mihaila

Curr. Issues Mol. Biol. 2025, 47(9), 698; https://doi.org/10.3390/cimb47090698 - 28 Aug 2025

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients. Full article

(This article belongs to the Special Issue Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy)

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