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Upregulation of Circular RNA circATRNL1 to Sensitize Oral Squamous Cell Carcinoma to Irradiation.

ABSTRACT: Accumulating evidence has demonstrated that circular RNAs (circRNAs) play important roles in regulating gene expression involved in tumor development. However, the role of circRNAs in modulating the radiosensitivity of oral squamous cell carcinoma (OSCC) and its potential mechanisms have not been documented. We performed high-throughput RNA sequencing (RNA-seq) to investigate the circRNA expression profile in OSCC patients and discovered that the circATRNL1 expression was significantly downregulated and closely related to tumor progression. The circATRNL1 was structurally validated via Sanger sequencing, RNase R treatment, and specific convergent and divergent primer amplification. Importantly, the expression levels of circATRNL1 decreased after irradiation treatment, and upregulation of circATRNL1 enhanced the radiosensitivity of OSCC through suppressing proliferation and the colony survival fraction, inducing apoptosis and cell-cycle arrest. Moreover, we observed that circATRNL1 could directly bind to microRNA-23a-3p (miR-23a-3p) and relieve inhibition for the target gene PTEN. In addition, the tumor radiosensitivity-promoting effect of circATRNL1 overexpression was blocked by miR-23a-3p in OSCC. Further experiments also showed that PTEN can reverse the inhibitory effect of OSCC radiosensitivity triggered by miR-23a-3p. We concluded that circANTRL1 may function as the sponge of miR-23a-3p to promote PTEN expression and eventually contributes to OSCC radiosensitivity enhancement. This study indicates that circANTRL1 may be a novel therapeutic target to improve the efficiency of radiotherapy in OSCC.

SUBMITTER: Chen G

PROVIDER: S-EPMC7005496 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Upregulation of Circular RNA circATRNL1 to Sensitize Oral Squamous Cell Carcinoma to Irradiation.

Chen Guanhui G Li Yiming Y He Yi Y Zeng Binghui B Yi Chen C Wang Chao C Zhang Xiliu X Zhao Wei W Yu Dongsheng D

Molecular therapy. Nucleic acids 20200110

Accumulating evidence has demonstrated that circular RNAs (circRNAs) play important roles in regulating gene expression involved in tumor development. However, the role of circRNAs in modulating the radiosensitivity of oral squamous cell carcinoma (OSCC) and its potential mechanisms have not been documented. We performed high-throughput RNA sequencing (RNA-seq) to investigate the circRNA expression profile in OSCC patients and discovered that the circATRNL1 expression was significantly downregul ...[more]

PMID: 32032888

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Project description:BackgroundCircular RNAs (circRNAs) are involved in the pathogenesis of several diseases. Among oral maxillofacial cancers, oral squamous cell carcinoma (OSCC) has the highest incidence. However, the role of circRNAs in OSCC is still not clear. The aim of our study was to evaluate the circRNA expression profile in OSCC and explore further the potential role of circRNAs in the pathogenesis of OSCC.MethodsCircRNA sequencing was performed in 6 pairs of samples of OSCC and normal oral mucosal tissues. Expression of selected circRNAs was validated by qRT-PCR. GO and KEGG analyses were performed and binding relationships between circRNAs and miRNAs were predicted. The hsa_circ_0001766/miR-877-3p/VEGFA axis was selected to further elucidate its role in OSCC.ResultsWe showed that there were 122 differentially expressed (DE) circRNAs. Eight out of 10 selected circRNAs were validated by qRT-PCR. GO and KEGG analyses indicated that the identified DE circRNAs might be involved in the progression of OSCC. Then, after identification by Sanger sequencing and RNase R assay, the upregulated hsa_circ_0001766 was selected to investigate its potential role in OSCC. Bioinformatics analysis showed that hsa_circ_0001766 might act as a competing endogenous RNA (ceRNA) that sponged miR-877-3p to upregulate VEGFA expression. We selected OSCC cell lines SCC9 and SCC25. PCR results showed that the expression of hsa_circ_0001766 and VEGFA was upregulated in SCC9 and SCC25. Subsequently, using western blot, PCR, CCK8, and colony formation assays, we found that knocking down circRNA0001766 inhibited the expression of VEGFA and the proliferation of OSCC cells. Following this, miR-877-3p inhibitor reversed the inhibitory effect of si-hsa_circ_0001766 on expression of VEGFA and proliferation of OSCC cells.ConclusionsIn conclusion, our study revealed the possible role of circRNAs in the pathogenesis of OSCC, and identified the potential role of the hsa_circ_0001766/miR-877-3p/VEGFA axis in OSCC progression.

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Upregulation of Circular RNA circATRNL1 to Sensitize Oral Squamous Cell Carcinoma to Irradiation.

Publications

Upregulation of Circular RNA circATRNL1 to Sensitize Oral Squamous Cell Carcinoma to Irradiation.

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