Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-03-11 DOI:10.1093/carcin/bgad082
Shuai Chen, Yingrui Zong, Zhenzhen Hou, Zhifen Deng, Zongping Xia
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Abstract

Objectives: Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral and maxillofacial regions with an increasing incidence rate. Circular RNA (circRNA) is a recently discovered long-chain non-coding RNA family member. The objective of this study was to analyze the role of circ_0068162 in OSCC development.

Methods: We downloaded sample data GSE145608 from the Gene Expression Omnibus database. Online databases Starbase, TargetScan and miRDB were used to predict the target microRNAs (miRNAs) and genes. Cell viability and proliferation were assessed using the CCK-8 and EdU assays, respectively. Cell migration and invasion abilities were detected using transwell assay. The double luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction relationship between the identified target molecules. RNase R and actinomycin D treatment were performed to analyze the stability of circ_0068162.

Results: We found that circ_0068162 was overexpressed in the cytoplasm of OSCC cells and clinical OSCC tissues. Knockdown of circ_0068162 inhibited the growth, migration and invasion of OSCC cells. We also identified miR-186 as the target miRNA of circ_0068162, and JAG1 and JAG2 as the target genes of miR-186. The miR-186 inhibitor rescued the effects of sh-circ_0068162 and JAG1/JAG2 overexpression rescued the effects of miR-186 mimic in OSCC cells. Furthermore, ESRP1 promoted the biosynthesis of circ_0068162.

Conclusions: The circ_0068162/miR-186/JAGs/ESRP1 feedback loop is closely related to OSCC development.

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剪接因子ESRP1衍生circ_0068162通过miR-186/JAG轴促进口腔鳞状细胞癌的进展。
背景:口腔鳞状细胞癌(Oral squamous cell carcinoma, OSCC)是口腔颌面部常见的恶性肿瘤,发病率呈上升趋势。环状RNA (circRNA)是一种新发现的长链非编码RNA家族成员。本研究的目的是分析circ_0068162在OSCC发展中的作用。方法:从Gene Expression Omnibus数据库下载样本数据GSE145608。使用在线数据库starbase、TargetScan和miRDB预测目标mirna和基因。分别用CCK-8和EdU测定细胞活力和增殖能力。transwell法检测细胞迁移和侵袭能力。双荧光素酶报告基因和RIP实验验证鉴定的靶分子之间的相互作用关系。采用RNase R和放线菌素D处理,分析circ_0068162的稳定性。结果:我们发现circ_0068162在OSCC细胞和临床OSCC组织的细胞质中过表达。敲低circ_0068162可抑制OSCC细胞的生长、迁移和侵袭。我们还发现miR-186是circ_0068162的靶miRNA, JAG1和JAG2是miR-186的靶基因。miR-186抑制剂恢复了sh-circ_0068162的作用,JAG1/JAG2过表达恢复了miR-186模拟物在OSCC细胞中的作用。此外,ESRP1促进了circ_0068162的生物合成。结论:circ_0068162/miR-186/JAGs/ESRP1反馈回路与OSCC的发展密切相关。
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4.30%
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567
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