Long-read RNA sequencing enables full-length chimeric transcript annotation of transposable elements in lung adenocarcinoma

作者：Yang Li, Yahui Liu, Yingxin Xie, Yaxuan Wang, Jing Wang, Huan Wang, Xia Lin, Dan Xie · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-025-13888-5 · 被引用次数：9 · 研究领域：Chromosomal and Genetic Variations、RNA modifications and cancer、Genomic variations and chromosomal abnormalities

BACKGROUND: Transposable elements (TEs), which constitute nearly half of the human genome, have long been regarded as genomic "dark matter". However, their reactivation in tumor cells, resulting in the production of TE-chimeric transcripts (TCTs), has emerged as a potential driver of cancer progression. The complexity and full extent of these transcripts remain elusive, largely due to the limitations of short-read next-generation sequencing technologies. These methods have struggled to comprehensively capture the diversity and structure of TCTs, particularly those involving short interspersed nuclear elements (SINEs) or closely co-transcribed TEs. METHODS: Leveraging full-length cDNA sequencing technology based on nanopore sequencing platform, we developed a customized pipeline for identifying and quantifying TCTs in 19 lung adenocarcinoma (LUAD) cell lines. The short-read RNA-seq dataset from a LUAD corhort (~ 200 tumor samples) was employed to validate the identified TCTs and explore their association with tumor progression. To assess the functional roles of a specific TCTs, cell migration and cell proliferation assays were performed. RESULTS: We uncovered 208 unique TCT candidates in the LUAD cell lines. Our approach allowed for the identification of cryptic promoters and terminators within non-transposing TEs. Notably, we identified a chimeric transcript involving MIR_HKDC1, which appears to play a significant role in the progression of LUAD. Furthermore, the expression o...