Xian Jiaotong University, Xi'an, China.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Sci Rep. 2017 Feb 15;7:42819. doi: 10.1038/srep42819.
Whole transcriptome analyses of next generation RNA sequencing (RNA-Seq) data from human cancer samples reveled thousands of uncharacterized non-coding RNAs including long non-coding RNA (lncRNA). Recent studies indicated that lncRNAs are emerging as crucial regulators in cancer processes and potentially useful as biomarkers for cancer diagnosis and prognosis. To delineate dysregulated lncRNAs in lung cancer, we analyzed RNA-Seq data from 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues. FAM83H-AS1, one of the top dysregulated lncRNAs, was found to be overexpressed in tumors relative to normal lung and significantly associated with worse patient survival in LUAD. We verified this diagnostic/prognostic potential in an independent cohort of LUAD by qRT-PCR. Cell proliferation, migration and invasion were decreased after FAM83H-AS1 knockdown using siRNAs in lung cancer cells. Flow cytometry analysis indicated the cell cycle was arrested at the G2 phase after FAM83H-AS1 knockdown. Mechanistically, we found that MET/EGFR signaling was regulated by FAM83H-AS1. Our study indicated that FAM83H-AS1 plays an important role in lung tumor progression and may be potentially used as diagnostic/prognostic marker. Further characterization of this lncRNA may provide a novel therapeutic target impacting MET/EGFR signaling.
对来自人类癌症样本的下一代 RNA 测序（RNA-Seq）数据的全转录组分析揭示了数千种未被表征的非编码 RNA，包括长非编码 RNA（lncRNA）。最近的研究表明，lncRNA 正在成为癌症过程中的重要调节因子，并可能作为癌症诊断和预后的有用生物标志物。为了描绘肺癌中失调的 lncRNA，我们分析了来自 461 例肺腺癌（LUAD）和 156 例正常肺组织的 RNA-Seq 数据。在肿瘤中相对正常肺组织表达上调的 FAM83H-AS1 是 top 失调的 lncRNA 之一，与 LUAD 患者的生存预后显著相关。我们通过 qRT-PCR 在独立的 LUAD 队列中验证了这种诊断/预后潜力。在肺癌细胞中使用 siRNA 敲低 FAM83H-AS1 后，细胞增殖、迁移和侵袭能力降低。流式细胞术分析表明，FAM83H-AS1 敲低后细胞周期被阻滞在 G2 期。从机制上讲，我们发现 FAM83H-AS1 调节 MET/EGFR 信号。我们的研究表明，FAM83H-AS1 在肺肿瘤进展中起着重要作用，可能潜在地用作诊断/预后标志物。进一步表征这种 lncRNA 可能提供一个影响 MET/EGFR 信号的新的治疗靶点。
