敲低长链非编码 RNA IGF2BP2-AS1 通过 Wnt/β-catenin 通路抑制口腔鳞状细胞癌细胞的增殖和迁移。
Knockdown of lncRNA IGF2BP2-AS1 inhibits proliferation and migration of oral squamous cell carcinoma cells via the Wnt/β-catenin pathway.
机构信息
Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.
Department of Stomatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
出版信息
J Oral Pathol Med. 2022 Mar;51(3):272-280. doi: 10.1111/jop.13248. Epub 2021 Nov 29.
BACKGROUND
Long non-coding RNA IGF2BP2 antisense RNA1 (lncRNA IGF2BP2-AS1) has been used to predict the overall survival rate of lung squamous cell carcinoma. This research aims to investigate the effect of IGF2BP2-AS1 in oral squamous cell carcinoma (OSCC).
METHODS
The TCGA database was applied to evaluate the level of IGF2BP2-AS1 and its correlation with the clinicopathological characteristics of OSCC. The levels of IGF2BP2-AS1 in 30 OSCC and 20 normal tissue samples were detected by RT-qPCR. The distributions of IGF2BP2-AS1 in two OSCC cell lines (ie, Cal27 and SCC9) were detected by FISH. Colony formation, flow cytometry, wound-healing, transwell, and Western blotting analyses were used for evaluating the effect of IGF2BP2-AS1 on OSCC progression.
RESULTS
In comparison with the normal tissue samples, OSCC showed higher expression of IGF2BP2-AS1. High expression of IGF2BP2-AS1 was associated with poor survival in OSCC patients. Results of FISH showed that IGF2BP2-AS1 was mainly present in the cytoplasm. Further in vitro functional tests demonstrated that downregulation of IGF2BP2-AS1 in Cal27 and SCC9 cells significantly inhibited cell proliferation and migration, leading to cell-cycle arrest and cell apoptosis. Western blotting showed that expressions of β-catenin, Cyclin D1, Bcl-2, and MMP2 were downregulated, whereas Bax was upregulated following knockdown of IGF2BP2-AS1. The inhibitory effect of knockdown of IGF2BP2-AS1 on migration could be partially reversed by the Wnt/β-catenin pathway stimulator LiCl.
CONCLUSION
Our results suggest that knockdown of IGF2BP2-AS1 suppresses cell growth, migration and promotes apoptosis in OSCC cells, providing a new molecular target for OSCC.
背景
长链非编码 RNA IGF2BP2 反义 RNA1（lncRNA IGF2BP2-AS1）已被用于预测肺鳞状细胞癌的总生存率。本研究旨在探讨 IGF2BP2-AS1 在口腔鳞状细胞癌（OSCC）中的作用。
方法
应用 TCGA 数据库评估 IGF2BP2-AS1 的水平及其与 OSCC 临床病理特征的相关性。通过 RT-qPCR 检测 30 例 OSCC 和 20 例正常组织样本中的 IGF2BP2-AS1 水平。通过 FISH 检测两种 OSCC 细胞系（即 Cal27 和 SCC9）中 IGF2BP2-AS1 的分布。通过集落形成、流式细胞术、划痕愈合、Transwell 和 Western blot 分析评估 IGF2BP2-AS1 对 OSCC 进展的影响。
结果
与正常组织样本相比，OSCC 中 IGF2BP2-AS1 的表达较高。IGF2BP2-AS1 高表达与 OSCC 患者的生存不良相关。FISH 结果显示 IGF2BP2-AS1 主要存在于细胞质中。进一步的体外功能试验表明，下调 Cal27 和 SCC9 细胞中的 IGF2BP2-AS1 显著抑制细胞增殖和迁移，导致细胞周期停滞和细胞凋亡。Western blot 显示，下调 IGF2BP2-AS1 后，β-catenin、Cyclin D1、Bcl-2 和 MMP2 的表达下调，而 Bax 的表达上调。IGF2BP2-AS1 敲低对迁移的抑制作用可被 Wnt/β-catenin 通路激动剂 LiCl 部分逆转。
结论
我们的结果表明，下调 IGF2BP2-AS1 抑制 OSCC 细胞的生长、迁移并促进细胞凋亡，为 OSCC 提供了一个新的分子靶点。
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