Liu Dejun, Zhao Jing, Wang Huiling, Li Hui, Li Yanjie, Qin Wangsen
Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, People's Republic of China.
Onco Targets Ther. 2020 Nov 20;13:11975-11990. doi: 10.2147/OTT.S279798. eCollection 2020.
Long intergenic non-protein coding RNA 519 () promotes the development of lung squamous cell carcinoma. In this study, we detected the expression of in tongue squamous cell carcinoma (TSCC) and examined its clinical significance. Additionally, the regulatory effects of on behaviors of TSCC tumor cells were explored through functional experiments. Finally, mechanistic studies were performed to elucidate the molecular events underlying the tumor-promoting actions of in TSCC.
The expression of in TSCC tissues and cell lines was determined using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 assay, flow cytometric analysis, cell migration and invasion assays and xenograft tumor model analyses were used to detect TSCC cell proliferation, apoptosis, migration and invasion and in vivo tumor growth, respectively. Mechanistic studies were performed using bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay and rescue experiments.
was overexpressed in both TSCC tissues and cell lines. A high level was associated with poor overall survival in patients with TSCC. In vitro, played cancer-promoting roles in TSCC progression by facilitating cell proliferation, migration and invasion and restraining cell apoptosis. In vivo, downregulation resulted in decreased TSCC tumor growth. Mechanistically, acted as a competing endogenous RNA for microRNA-876-3p (miR-876-3p), which directly targets metastasis associated with colon cancer-1 (), in TSCC cells. upregulated the expression of in TSCC cells by sequestering miR-876-3p. Rescue experiments further affirmed that miR-876-3p inhibition or overexpression mitigated the inhibitory influences of depletion on cell proliferation, migration and invasion and neutralized the promoting actions of knockdown on cell apoptosis in TSCC.
aggravated the oncogenicity of TSCC by regulating the miR-876-3p/MACC1 axis. Our findings suggest that the LINC00519/miR-876-3p/MACC1 pathway may be an underlying therapeutic target in TSCC.
长链基因间非编码RNA 519（LINC00519）促进肺鳞状细胞癌的发展。在本研究中，我们检测了LINC00519在舌鳞状细胞癌（TSCC）中的表达，并探讨其临床意义。此外，通过功能实验研究了LINC00519对TSCC肿瘤细胞行为的调控作用。最后，进行机制研究以阐明LINC00519在TSCC中促肿瘤作用的分子机制。
采用定量逆转录-聚合酶链反应检测TSCC组织和细胞系中LINC00519的表达。分别使用细胞计数试剂盒-8检测、流式细胞术分析、细胞迁移和侵袭实验以及异种移植瘤模型分析来检测TSCC细胞的增殖、凋亡、迁移和侵袭以及体内肿瘤生长情况。通过生物信息学分析、RNA免疫沉淀实验、荧光素酶报告基因实验和挽救实验进行机制研究。
LINC00519在TSCC组织和细胞系中均过表达。TSCC患者中LINC00519高表达与总体生存率低相关。在体外，LINC00519通过促进细胞增殖、迁移和侵袭以及抑制细胞凋亡在TSCC进展中发挥促癌作用。在体内，LINC00519下调导致TSCC肿瘤生长减缓。机制上，LINC00519作为微小RNA-876-3p（miR-876-3p）的竞争性内源性RNA，在TSCC细胞中，miR-876-3p直接靶向结肠癌相关转移因子1（MACC1）。LINC00519通过隔离miR-876-3p上调TSCC细胞中MACC1的表达。挽救实验进一步证实，抑制miR-876-3p或过表达LINC00519可减轻LINC00519缺失对细胞增殖、迁移和侵袭的抑制作用，并抵消LINC00519敲低对TSCC细胞凋亡的促进作用。
LINC00519通过调节miR-876-3p/MACC1轴加重了TSCC的致癌性。我们的研究结果表明，LINC00519/miR-876-3p/MACC1通路可能是TSCC潜在的治疗靶点。
