Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Key laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Ministry of Education, Harbin, China.
Ann Med. 2024 Dec;56(1):2430029. doi: 10.1080/07853890.2024.2430029. Epub 2024 Nov 25.
Lung adenocarcinoma is the most common type of lung cancer, accounting for approximately 40% of all lung cancer cases, and has the highest incidence among lung cancer subtypes. Recent studies have suggested that long non-coding RNAs (lncRNAs) play a crucial role in the initiation and progression of lung adenocarcinoma.
Based on integrative analysis through databases, we screened Long intergenic non-protein coding RNA 00839 (LINC00839) as one of the most highly upregulated lncRNAs in lung adenocarcinoma. and experiments demonstrated that LINC00839 promotes lung adenocarcinoma proliferation, migration, and invasion and that it is present in exosomes secreted by lung adenocarcinoma cells.
In the cytoplasm, LINC00839 regulates the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway by acting as a molecular sponge of miR-17-5p, thereby influencing the biological behavior of lung adenocarcinoma cells. LINC00839 binds to Polypyrimidine tract binding protein 1 (PTBP1) in the nucleus to regulate the nuclear translocation of NF-κB p65 molecules and, consequently, the transcription of downstream molecules.
Our study confirmed that LINC00839 promotes the biological progression of lung adenocarcinoma by performing dual roles in the cytoplasm and nucleus to co-regulate the NF-κB signaling pathway.
肺腺癌是最常见的肺癌类型,约占所有肺癌病例的 40%,在肺癌亚型中发病率最高。最近的研究表明,长非编码 RNA(lncRNA)在肺腺癌的发生和发展中起着关键作用。
我们通过数据库的综合分析,筛选出长非编码 RNA 00839(LINC00839)作为肺腺癌中上调最明显的 lncRNA 之一。并通过实验证明,LINC00839 促进肺腺癌的增殖、迁移和侵袭,并且存在于肺腺癌细胞分泌的外泌体中。
在细胞质中,LINC00839 通过作为 miR-17-5p 的分子海绵来调节 Toll 样受体 4(TLR4)/NF-κB 信号通路,从而影响肺腺癌细胞的生物学行为。LINC00839 在核内与多嘧啶 tract 结合蛋白 1(PTBP1)结合,调节 NF-κB p65 分子的核转位,进而调控下游分子的转录。
我们的研究证实,LINC00839 通过在细胞质和核内发挥双重作用共同调节 NF-κB 信号通路,促进肺腺癌的生物学进展。