Otolaryngology Head and Neck Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang 050005, Hebei, China; Otolaryngology Head and Neck Surgery Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China.
Otolaryngology Head and Neck Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang 050005, Hebei, China.
Pathol Res Pract. 2020 Apr;216(4):152877. doi: 10.1016/j.prp.2020.152877. Epub 2020 Feb 13.
Long noncoding RNAs (lncRNAs) play crucial role in formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The research aims to investigate the biofunction of a novel lncRNA in LSCC.
qRT-PCR, BGS, and MSP methods were employed to measure the relative expression level and methylation status of LINC00886. Additionally, we examined the effects of LINC00886 on cells proliferation and invasion using LINC00886 over-expression. Nude mouse xenograft models were conducted to assess LINC00886 effects on LSCC growth in vivo. High-throughput sequencing technology and Western blot assay were carried out to have an in-depth study of the downstream target genes and signaling pathways in which LINC00886 may participate.
The remarkable downregulation of LINC00886 was observed in tumor tissues and laryngeal cancer cell lines. The significant decrease of LINC00886 was correlated with pathological grade in LSCC tissues. The expression level of LINC00886 in laryngeal cancer cell lines was significantly reversed by 5-Aza-dC. The occurrence of aberrant methylation events in the LINC00886 TSS was more responsible for the down-expression of LINC00886. Over-expression of LINC00886 dramatically mitigated cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. LINC00886 may be associated with VEGFA/PI3K/AKT signaling pathways and epithelial-mesenchymal transition (EMT) process.
We provide the first evidence of the involvement of LINC00886 in laryngeal carcinoma, which was downregulated due to methylation of the promoter region and served as tumor suppressor genes. LINC00886 is expected to become a novel biomarker in laryngeal carcinoma.
长链非编码 RNA（lncRNA）在肿瘤的发生和发展中起着至关重要的作用。DNA 甲基化已越来越被认为是表观遗传改变的频繁事件之一，也是基因失活的主要机制之一。本研究旨在探讨一种新型 lncRNA 在喉鳞状细胞癌（LSCC）中的生物学功能。
采用 qRT-PCR、BGS 和 MSP 方法检测 LINC00886 的相对表达水平和甲基化状态。此外，我们通过过表达 LINC00886 来检测 LINC00886 对细胞增殖和侵袭的影响。构建裸鼠异种移植模型，评估 LINC00886 在体内对 LSCC 生长的影响。采用高通量测序技术和 Western blot 检测深入研究 LINC00886 可能参与的下游靶基因和信号通路。
在肿瘤组织和喉癌细胞系中观察到 LINC00886 的显著下调。LINC00886 的表达水平与 LSCC 组织的病理分级显著相关。5-Aza-dC 可显著逆转喉癌细胞系中 LINC00886 的表达水平。LINC00886 TSS 处异常甲基化事件的发生更导致 LINC00886 的下调表达。过表达 LINC00886 可显著抑制体外细胞增殖、迁移和侵袭，并抑制体内肿瘤生长。LINC00886 可能与 VEGFA/PI3K/AKT 信号通路和上皮-间质转化（EMT）过程有关。
本研究首次证明 LINC00886 参与喉癌的发生，其因启动子区域甲基化而下调，发挥抑癌基因的作用。LINC00886 有望成为喉癌的一种新型生物标志物。
