Department of Stomatology, Affiliated Hospital of Ji'ning Medical University, Ji'ning, Shandong, China.
Department of Stomatology, Shandong Energy Zibo Mining Group Co. Ltd Central Hospital, Zibo, Shandong, China.
J Oral Pathol Med. 2018 May;47(5):468-476. doi: 10.1111/jop.12677. Epub 2018 Mar 30.
Aimed at underlying the molecular regulatory mechanism and overall biological functions of LINC00511 in tongue squamous cell carcinoma (TSCC).
The expression level of LINC00511 was examined by QRT-PCR. In particular, Tca-8113 cell line was selected for subsequent experiments, in which the expression level of LINC00511 was the most significant. Meanwhile, the effects of LINC00511 on cells proliferation, cell cycle distribution, and invasion of TSCC cells were explored using RNA knockdown tools with CCK-8, flow cytometry analysis, colony formation, and transwell assay. Further, bioinformatic analysis and the dual-luciferase reporter assay both were conducted to invalidate the ceRNAs regulatory mechanism of LINC00511 in TSCC.
LINC00511 was obviously upregulated in TSCC tissues and cell lines. Moreover, it was found that LINC00511 served as a competing endogenous RNA (ceRNA) through sponging miR-765 and ultimately modulated the derepression of laminin subunit gamma 2 (LAMC2). The inhibitory effects of miR-765 on TSCC cells proliferation, invasion as well as cell cycle distribution can be restored by the ectopic overexpression of LINC00511. Additionally, the restored capacity of LINC00511 promoted the expression of LAMC2, which was a downstream target of miR-765 and can be negatively regulated by miR-765.
A novel molecular axis of LINC00511/miR-765/LAMC2 was investigated to regulate the tumor development of TSCC. LINC00511 promoted the expression of LAMC2 via the ceRNA mechanism of sponging miR-765. The ceRNA regulatory network provided a novel understanding of TSCC pathogenesis and also shed light on exploiting the new field of lncRNA-directed therapy against TSCC.
旨在阐明 LINC00511 在舌鳞状细胞癌（TSCC）中的分子调控机制和整体生物学功能。
通过 QRT-PCR 检测 LINC00511 的表达水平。特别是选择 Tca-8113 细胞系进行后续实验，其中 LINC00511 的表达水平最为显著。同时，使用 RNA 敲低工具通过 CCK-8、流式细胞术分析、集落形成和 Transwell 测定来研究 LINC00511 对 TSCC 细胞增殖、细胞周期分布和侵袭的影响。此外，通过生物信息学分析和双荧光素酶报告基因实验验证了 LINC00511 在 TSCC 中的 ceRNA 调控机制。
LINC00511 在 TSCC 组织和细胞系中明显上调。此外，研究发现 LINC00511 通过海绵吸附 miR-765 作为竞争性内源 RNA (ceRNA)，最终调节层粘连蛋白亚基γ 2 (LAMC2)的去抑制。miR-765 对 TSCC 细胞增殖、侵袭和细胞周期分布的抑制作用可以通过 LINC00511 的异位过表达得到恢复。此外，LINC00511 的恢复能力促进了 miR-765 的下游靶标 LAMC2 的表达，LAMC2 可被 miR-765 负调控。
研究了 LINC00511/miR-765/LAMC2 的新分子轴，以调节 TSCC 的肿瘤发展。LINC00511 通过海绵吸附 miR-765 的 ceRNA 机制促进 LAMC2 的表达。ceRNA 调控网络为 TSCC 发病机制提供了新的认识，也为利用 lncRNA 指导的治疗方法治疗 TSCC 开辟了新的领域。
