Wu Qingwei, Zhao Yingying, Shi Runjie, Wang Tao
Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Cancer Manag Res. 2021 May 20;13:4103-4114. doi: 10.2147/CMAR.S305544. eCollection 2021.
Accumulating evidence shows that lncRNAs are widely involved cellular processes of various tumors. The aim of this study was to explore the potential role and molecular mechanism of lncRNA SNHG16 in nasopharyngeal carcinoma (NPC).
SNHG16, miR-520a-3p, and MAPK1 levels were measured by RT-qPCR assay. CCK-8, colony formation, transwell, and flow cytometry assays were adopted to analyze the proliferation, migration, invasion, and apoptosis of NPC cell lines (SUNE1 and 5-8F). Murine xenograft model was used to investigate tumor growth and metastasis in vivo. Immunohistochemical staining was employed to evaluate the levels of Bcl-2, cleaved caspase-3, Bax, and Ki-67. Dual-luciferase reporter assays were conducted to analyze the binding ability between miR-520a-3p and SNHG16 or MAPK1.
SNHG16 was overexpressed in NPC tissues and cells. High SNHG16 expression indicated a poor prognosis. SNHG16 knockdown could cause significant inhibition on cell proliferation and metastasis, induce cell apoptosis in NPC cells, and repressed tumor growth and metastasis in vivo. Additionally, SNHG16 could directly bind to miR-520a-3p, thus positively regulating MAPK1 expression. Moreover, functional analysis indicated that miR-520a-3p exerted a tumor-suppressing role in NPC progression. Rescue assays demonstrated that MAPK1 upregulation could abrogate the inhibitory effects on NPC cell proliferation and metastasis, as well as the promoting effects on NPC cell apoptosis caused by SNHG16 knockdown. In conclusion, SNHG16 contributed to the proliferation and metastasis of NPC cells by modulating the miR-520a-3p/MAPK1 axis.
These results suggest that SNHG16 acts as an oncogene in the progression of NPC via modulating the miR-520a-3p/MAPK1 axis.
越来越多的证据表明，长链非编码RNA（lncRNAs）广泛参与各种肿瘤的细胞过程。本研究旨在探讨lncRNA SNHG16在鼻咽癌（NPC）中的潜在作用及分子机制。
采用逆转录-定量聚合酶链反应（RT-qPCR）检测SNHG16、miR-520a-3p和丝裂原活化蛋白激酶1（MAPK1）水平。采用细胞计数试剂盒-8（CCK-8）、集落形成、Transwell和流式细胞术分析鼻咽癌细胞系（SUNE1和5-8F）的增殖、迁移、侵袭和凋亡。利用小鼠异种移植模型研究体内肿瘤生长和转移情况。采用免疫组织化学染色评估Bcl-2、裂解的半胱天冬酶-3、Bax和Ki-67的水平。进行双荧光素酶报告基因检测，分析miR-520a-3p与SNHG16或MAPK1之间的结合能力。
SNHG16在鼻咽癌组织和细胞中高表达。SNHG16高表达提示预后不良。敲低SNHG16可显著抑制细胞增殖和转移，诱导鼻咽癌细胞凋亡，并抑制体内肿瘤生长和转移。此外，SNHG16可直接与miR-520a-3p结合，从而正向调节MAPK1表达。此外，功能分析表明，miR-520a-3p在鼻咽癌进展中发挥肿瘤抑制作用。挽救实验表明，上调MAPK1可消除敲低SNHG16对鼻咽癌细胞增殖和转移的抑制作用，以及对鼻咽癌细胞凋亡的促进作用。总之，SNHG16通过调节miR-520a-3p/MAPK1轴促进鼻咽癌细胞的增殖和转移。
这些结果表明，SNHG16通过调节miR-520a-3p/MAPK1轴在鼻咽癌进展中作为癌基因发挥作用。
