Circular RNA ITCH Suppresses Cell Proliferation but Induces Apoptosis in Oral Squamous Cell Carcinoma by Regulating miR-421/PDCD4 Axis

环状 RNA ITCH 通过调节 miR-421/PDCD4 轴抑制口腔鳞状细胞癌细胞增殖并诱导细胞凋亡

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作者:Chunbo Hao #, Kaixin Wangzhou #, Zhengeng Liang, Cheng Liu, Linlin Wang, Lei Gong, Yi Tan, Conghui Li, Zhiying Lai, Guangwei Hu

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

Conclusion

In conclusion, our study reveals that circ-ITCH serves as a tumor suppressor in OSCC partly by regulating miR-421/PDCD4 axis.

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.

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