环状RNA ITCH通过调控miR-421/PDCD4轴抑制口腔鳞状细胞癌的细胞增殖但诱导其凋亡。
Circular RNA ITCH Suppresses Cell Proliferation but Induces Apoptosis in Oral Squamous Cell Carcinoma by Regulating miR-421/PDCD4 Axis.
作者信息
Hao Chunbo, Wangzhou Kaixin, Liang Zhengeng, Liu Cheng, Wang Linlin, Gong Lei, Tan Yi, Li Conghui, Lai Zhiying, Hu Guangwei
机构信息
Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570011, Hainan Province, People's Republic of China.
School of Management, Hainan Medical University, Haikou 570011, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Jul 12;12:5651-5658. doi: 10.2147/CMAR.S258887. eCollection 2020.
BACKGROUND
Circular RNAs (circRNAs), a group of covalently closed non-coding RNAs, serve critical regulatory roles in many human cancers, including oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the functional role of circular RNA ITCH (circ-ITCH) in OSCC and the underlying mechanisms.
METHODS
RT-qPCR analysis was applied to detect the expression levels of circ-ITCH in OSCC tissues and cell lines. MTT assay and flow cytometer analysis were used to evaluate the effects of circ-ITCH overexpression on the proliferation and apoptosis of OSCC cells. Bioinformatics analysis and dual-luciferase reporter assay were applied to determine the binding relation between circ-ITCH and miR-421 as well as PDCD4 mRNA and miR-421.
RESULTS
Our results showed that circ-ITCH expression was remarkably decreased in OSCC tissues and cell lines. Low circ-ITCH expression was strongly associated with adverse clinicopathological characteristics of OSCC patients. Moreover, functional assays demonstrated that circ-ITCH overexpression significantly inhibited OSCC cell proliferation and induced cell apoptosis. Our data further uncovered that circ-ITCH could bind directly to miR-421 and block its repression on PDCD4 in OSCC. MiR-421 expression was significantly increased in OSCC tissues and was inversely correlated with circ-ITCH expression. Notably, miR-421 restoration blocked the tumor-suppressive role of circ-ITCH in OSCC cells.
CONCLUSION
In conclusion, our study reveals that circ-ITCH serves as a tumor suppressor in OSCC partly by regulating miR-421/PDCD4 axis.
背景
环状RNA（circRNAs）是一类共价闭合的非编码RNA，在包括口腔鳞状细胞癌（OSCC）在内的多种人类癌症中发挥关键的调控作用。本研究旨在探讨环状RNA ITCH（circ-ITCH）在OSCC中的功能作用及其潜在机制。
方法
应用RT-qPCR分析检测OSCC组织和细胞系中circ-ITCH的表达水平。采用MTT法和流式细胞仪分析评估circ-ITCH过表达对OSCC细胞增殖和凋亡的影响。应用生物信息学分析和双荧光素酶报告基因检测确定circ-ITCH与miR-421以及PDCD4 mRNA与miR-421之间的结合关系。
结果
我们的结果显示，circ-ITCH在OSCC组织和细胞系中的表达显著降低。circ-ITCH低表达与OSCC患者不良的临床病理特征密切相关。此外，功能分析表明，circ-ITCH过表达显著抑制OSCC细胞增殖并诱导细胞凋亡。我们的数据进一步发现，circ-ITCH可以直接与miR-421结合，并在OSCC中阻断其对PDCD4的抑制作用。miR-421在OSCC组织中的表达显著增加，且与circ-ITCH表达呈负相关。值得注意的是，miR-421的恢复阻断了circ-ITCH在OSCC细胞中的肿瘤抑制作用。
结论
总之，我们的研究表明，circ-ITCH在OSCC中作为肿瘤抑制因子，部分是通过调节miR-421/PDCD4轴发挥作用。
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