Crosstalk between alternative splicing and non-coding RNAs in hepatocellular carcinoma: from regulatory mechanism to therapeutic implications

Regulatory networks of non-coding RNAs in renal cell carcinogenesis and therapeutic intervention strategies

The Role of Alternative Splicing in Lung Cancer: Mechanisms, Regulators, and Therapeutic Implications

Lung cancer is characterized by profound molecular and clinical heterogeneity and remains the leading cause of cancer-related mortality worldwide. Its initiation and progression are shaped by complex genetic and epigenetic alterations that perturb key biological processes, including cell proliferation, apoptosis, metabolic reprogramming, invasion, metastasis, and immune evasion. Increasing evidence indicates that dysregulated alternative splicing (AS) represents a critical post-transcriptional regulatory mechanism involved in lung cancer pathogenesis. Although AS abnormalities are not the sole drivers of tumorigenesis, they contribute to malignant transformation, tumor progression, therapeutic resistance, and phenotypic plasticity, providing opportunities for biomarker development and therapeutic targeting. This review summarizes the multifaceted roles of AS in lung cancer biology, highlighting its contributions to tumor evolution, metastatic dissemination, and treatment resistance. Furthermore, subtype-specific AS landscapes between major lung cancer subtypes are discussed to elucidate their distinct molecular mechanisms and therapeutic implications. Representative AS-generated isoforms, including cluster of differentiation 44 variants (CD44v), are further discussed as examples of how aberrant splicing events regulate cancer stemness, tumor progression, and therapeutic responses. The regulatory mechanisms underlying CD44v generation, including upstream splicing factors and downstream signaling pathways, are also summarized. Collectively, this review highlights the emerging role of aberrant AS regulation in lung cancer and emphasizes its potential implications for biomarker discovery and precision therapeutic strategies targeting splicing dysregulation.

The emerging roles of non-coding RNAs in cancer.

This review examines how different types of ncRNAs contribute to cancer initiation, progression, and treatment resistance, and assesses their potential as diagnostic markers, prognostic factors, and therapeutic targets.

Alternative RNA Splicing in Cancer: Molecular Mechanisms, Functional Consequences, Biomarkers and Therapeutic Opportunities

This review integrates the molecular logic of splice-site selection with the cancer-specific mechanisms that perturb it, summarizes representative isoform switches across the hallmarks of cancer, evaluates emerging technologies and clinical biomarkers, and discusses the opportunities and constraints of translating splicing biology into precision oncology.

Non-Coding RNA Networks in Systemic Sclerosis: Roles in Pathogenesis, Biomarkers, and Therapeutic Opportunities

Non-coding RNAs have emerged as gene-regulatory molecules acting at epigenetic, transcriptional, and post-transcriptional levels. Among them, microRNAs are short RNA molecules consisting of approximately 22 nucleotides. Increased microRNA expression suppresses target protein expression, whereas decreased microRNA expression relieves this repression and can induce overexpression of target proteins. microRNAs integratively regulate highly complex biological processes, including cell proliferation, differentiation, apoptosis, morphogenesis, and immune responses. Therefore, alterations in microRNA expression profiles may be directly linked to the fundamental pathogenesis of systemic sclerosis (SSc), an autoimmune and fibrotic disease involving multiple organs. This focused narrative review examines microRNAs involved in SSc fibrosis, vasculopathy, and immune dysregulation; extracellular-particle-associated microRNAs; and circulating and hair-derived microRNAs as candidate biomarkers. It also summarizes evidence on long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), yRNAs, and PIWI-interacting RNAs (piRNAs). Finally, therapeutic perspectives, including microRNA mimics, antisense inhibitors, and broader RNA-targeted strategies, are discussed together with key challenges in validation and clinical translation.

Exosomal Non-Coding RNAs: Emerging regulators of the tumor microenvironment in gastrointestinal and hepatobiliary cancers.

Extracellular vesicle (EV)-associated non-coding RNAs (ncRNAs) are increasingly recognized as mediators of intercellular communication within the tumor microenvironment (TME), yet their mechanistic and translational significance varies substantially across gastrointestinal and hepatobiliary cancers. This narrative review, informed by a structured literature search, integrates evidence on EV-associated microRNAs, long non-coding RNAs, and circular RNAs in esophageal, gastric, colorectal, pancreatic, hepatocellular carcinoma, and cholangiocarcinoma. Rather than organizing the literature by RNA class or individual tumor type, we synthesize findings according to major TME functions, including immune remodeling, cancer-associated fibroblast activation, vascular remodeling, paracrine tumor-cell reprogramming, therapy resistance, and tumor-suppressive vesicular signaling. Recurrent mechanisms involve PTEN/PI3K/AKT, JAK/STAT, TGF-β/Smad, Wnt/β-catenin, and immune-checkpoint pathways, but the strength of evidence differs markedly among studies. Accordingly, mechanistic findings are distinguished from animal-model-supported, clinically correlated, preliminary, and biomarker-only evidence using a standardized descriptive framework. The review also highlights cholangiocarcinoma as an underrepresented but increasingly informative hepatobiliary model while avoiding generalization to broader biliary tract cancers when direct evidence is lacking. Major barriers to clinical translation include inconsistent EV isolation and characterization, uncertain vesicle-source attribution, limited validation of recipient-cell transfer and causal targets, small retrospective cohorts, and insufficient prospective validation. Overall, EV-ncRNAs represent promising mechanistic biomarkers and therapeutic targets, but rigorous source-specific validation and standardized analytical workflows are required before clinical implementation.