LINE-1 Transcript Heterogeneity in Non-Small Cell Lung Cancers Is Driven by Host Genomic Context and Conserved Functional Hotspots.
Simple Summary: Long interspersed element-1 sequences are normally silenced in healthy cells but frequently reactivated in cancer, where they contribute to genomic instability and transcriptional dysregulation. However, the determinants of their transcriptional heterogeneity in non-small cell lung c...
| Publicado en: | Cancers Vol. 18; no. 3; pp. 459 - 477 |
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| Autores principales: | , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
MDPI
Feb2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191588042&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191588042 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Feb2026 vid: 18 iid: 3 pid: 97109 pub: MDPI artinfo: ui: 191588042 191588042 191588042 10.3390/cancers18030459 191588042 ppf: 459 ppct: 18 formats: tig: atl: LINE-1 Transcript Heterogeneity in Non-Small Cell Lung Cancers Is Driven by Host Genomic Context and Conserved Functional Hotspots. aug: au: Wang, Yingshan Ramos, Kenneth S. affil: Center for Genomic and Precision Medicine, Texas A&M Institute of Biosciences and Technology, Houston, TX 77030, USA sug: subj: Carcinoma, Non-Small-Cell Lung Familial and Genetic Genome, Human Epigenomics Cell Line, Tumor Mutation Human Gene Expression Race Factors Sequence Analysis RNA Analysis T-Tests Descriptive Statistics Chromosome Mapping Funding Source ab: Simple Summary: Long interspersed element-1 sequences are normally silenced in healthy cells but frequently reactivated in cancer, where they contribute to genomic instability and transcriptional dysregulation. However, the determinants of their transcriptional heterogeneity in non-small cell lung cancer remain poorly defined. In this study, we systematically characterized locus-specific LINE-1 transcript expression across a large panel of non-small cell lung cancer cell lines to determine how genomic context shapes retrotransposon activity. We show that LINE-1 transcription is dominated by evolutionarily young elements and follows conserved chromosomal patterns across tumor subtypes, with the highest activity observed in lung squamous cell carcinoma. Importantly, LINE-1 expression is anchored by a small number of conserved genomic hotspot loci that remain active across tumor backgrounds and are located near cancer-relevant genes. These findings provide a genome-scale framework for understanding retrotransposon regulation in cancer and highlight conserved LINE-1 loci as potential markers of genome instability and regulatory vulnerability. Background: Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17–20% of the human genome. These retroelements are normally silenced early in embryonic development through epigenetic mechanisms and reawakened during oncogenesis, leading to transcriptional dysregulation, genomic instability, and immune evasion. Methods: In the present study, we categorized LINE-1 transcripts across 121 non-small cell lung cancer (NSCLC) cell lines from the Cancer Cell Line Encyclopedia (CCLE) by subfamily, length, orientation, chromosomal origin, and distribution. In addition, high-prevalence insertions were mapped to nearby genes to assess potential functional interactions. Results: LINE-1 transcript abundance and length in NSCLC were dominated by evolutionarily young subfamilies, particularly L1HS and L1PA2 through L1PA5. Chromosomal patterns were conserved across NSCLC subtypes, with modest enrichment of L1HS activity on Chromosome 4 and the X Chromosome. The lung squamous cell carcinoma (LSQCC) subtype exhibited the highest total levels of L1HS expression relative to other NSCLC subtypes. Race modestly influenced LINE-1 transcript abundance, with cell lines derived from self-identified African American individuals showing elevated overall LINE-1 and L1HS expression. Age showed a weak positive correlation with total LINE-1 abundance. Integrative analysis revealed recurrent hotspots at 22q12.1 and 20p11.21 that were transcriptionally active across subtypes and coincided with previously reported intact LINE-1 elements active in epithelial cancers. Recurrent insertions were located near cancer-associated genes, including RB1, NEDD4, FTO, LAMA2, NOD1, and KCNB2, implicating LINE-1 activity in cis-regulatory remodeling of oncogenic pathways. Conclusions: Together, these findings indicate that LINE-1 transcript heterogeneity in NSCLC is shaped by host genomic architecture and conserved functional hotspots, providing new insights into the mechanisms of genetic and epigenetic dysregulation associated with LINE-1 retroelements. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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