Transposable Element-Derived miR-28-5p and miR-708-5p: Exploring Potential Roles in Lung Cancer

Authors

Sergiu Chira
Cornelia Braicu
Stefan Strilciuc
George A Calin
Ioana Berindan-Neagoe

Publication Date

12-18-2025

Journal

Noncoding RNA

DOI

10.3390/ncrna11060081

PMID

41441397

PMCID

PMC12736026

PubMedCentral® Posted Date

12-18-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses.

Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. Further, we assessed the expression and methylation status of miR-28 and miR-708 host genes, LPP and TENM4, respectively, TENM4 using computational tools. Finaly, we searched for potential candidate tumor suppressor genes targeted by miR-28 and miR-708, which are downregulated in LUAD and LUSC.

Results: We found that intragenic L2-derived miR-28 and miR-708 are significantly upregulated in LUAD and LUSC. While TENM4 gene also displays a marked increase in expression in LUAD and LUSC, in tumor versus normal tissue, this difference is less obvious for the LPP gene. We suggest that such dysregulations in expression might be linked to specific methylation patterns of their genomic locations. Furthermore, we emphasize that miR-28 and miR-708 might contribute to lung cancer pathogenesis by targeting key tumor suppressor genes.

Conclusions: Alterations in the methylation status of L2-miRNAs genomic loci might result in elevated levels of miRNAs and subsequent targeting of tumor suppressor genes with potential implications in lung cancer pathogenesis.

Keywords

transposable elements, mir-28, mir-708, lung cancer

Published Open-Access

yes

Recommended Citation

Chira, Sergiu; Braicu, Cornelia; Strilciuc, Stefan; et al., "Transposable Element-Derived miR-28-5p and miR-708-5p: Exploring Potential Roles in Lung Cancer" (2025). Faculty, Staff and Student Publications. 5428.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5428