高通量测序技术在肿瘤的RNA可变剪接和选择性多聚腺苷酸化研究中的应用

打开文本图片集

中图分类号：R730.2 文献标志码：A 文章编号：1001-5779（2025）08-0739-11

DOI：10.3969/j.issn. 1001-5779.2025.08.003

Abstract：Alternativesplicing（AS）andalternative polyadenylation （APA）constitute pivotalpost-transcriptionalregulatory mechanisms in eukaryotes.By generating diverse mRNA isoforms，theysubstantially enhance thecomplexityof gene expresionand proteomicdiversity，playing criticalroles incellularphysiologicalandpathological processesparticularly exerting profound impactsontumor initiationand progresion.Theadventofhigh-throughputsequencing technologies has empoweredlarge-scaleinvestigationsofASandAPAevents.Due toitslimitations inreadlength，conventional secondgenerationsequencing （NGS）is difcult toaccuratelyanalyze complexand variable splicing pattrnsandAPA sites.The third-generationsequencing technology hasthecharacteristicsof long readlength andcan efectivelysolvethis problem. This review synthesizes advanes in applyingNGSandlong-read sequencing（LRS） to characterize tumor-asociated RNA alternativesplicingandalternativepolyadenylationevents.Literatureanalysis demonstrates thesignificantpotentialof long-read sequencing inoncologyresearch.Compared toNGS，LRS enablesmoreaccurate identification of complex alternative splicing paterns，precise mappingofsplicesitesandAPAsites，andresolutionofcomplete transcriptisoform structures，facilitating the discoveryof novel tumor-specificsplicing variantsand APA events.Long-read sequencing technology paves new path forcomprehensively mapping AS/APA landscapes intumors and elucidating their mechanistic roles in tumorigenesis.Futureapplications hold promisefor discovering novel tumor diagnostic biomarkers，prognostic indicators，and developing precision therapeutic strategies targetingRNA splicing regulation.

Key Words：Long-read sequencing；Alternative splicing；Alternative polyadenylation；Tumor

RNA结构对RNA功能至关重要，RNA结构变异能够调控基因表达和细胞功能，进而影响疾病的发生发展。（剩余21259字）