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环状RNA circ-SLC7A5作为竞争性内源性RNA影响食管鳞状细胞癌(ESCC)的细胞生物学行为。

Circular RNA circ-SLC7A5 Functions as a Competing Endogenous RNA to Impact Cell Biological Behaviors in Esophageal Squamous Cell Carcinoma (ESCC).

作者信息

Wang Lei, Hong Zhipeng

机构信息

Department of Cardiothoracic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou City, Zhejiang Province, China.

Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China.

出版信息

Cell Biochem Biophys. 2024 Mar;82(1):139-151. doi: 10.1007/s12013-023-01183-8. Epub 2023 Oct 9.

Abstract

BACKGROUND

Circular RNAs (circRNAs) have profound effects on establishment and pathogenesis of esophageal squamous cell carcinoma (ESCC). Here, we defined whether circRNA solute carrier family 7 member 5 (circ-SLC7A5, also called hsa_circ_0040796) is causally involved in the pathogenesis of ESCC.

METHODS

Circ-SLC7A5, microRNA (miR)-874-3p and coronin-1C (CORO1C) expression levels were gauged by qRT-PCR or immunoblotting. Cell functional phenotypes were tested by colony formation, EdU, flow cytometry, transwell and wound-healing assays. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were applied to ascertained circ-SLC7A5/miR-874-3p and miR-874-3p/CORO1C relationships.

RESULTS

Circ-SLC7A5 was highly expressed in human ESCC. Circ-SLC7A5 depletion impaired cell growth, migration, invasiveness, and promoted apoptosis. Circ-SLC7A5 knockdown diminished ESCC cell tumorigenicity. Mechanistically, circ-SLC7A5 contained a binding site for miR-874-3p. Also, miR-874-3p was responsible for circ-SLC7A5's function in ESCC cells. CORO1C was a direct miR-874-3p target. Circ-SLC7A5 functioned as a competing endogenous RNA (ceRNA) to control CORO1C by competing for shared miR-874-3p. Furthermore, CORO1C knockdown phenocopied miR-874-3p overexpression in impacting the biological behaviors of ESCC cells.

CONCLUSION

These findings identify circ-SLC7A5 as a crucial modulator of ESCC cells and establish a novel circ-SLC7A5/miR-874-3p/CORO1C ceRNA network in ESCC.

摘要

背景

环状RNA(circRNAs)对食管鳞状细胞癌(ESCC)的发生发展及发病机制具有深远影响。在此,我们确定环状RNA溶质载体家族7成员5(circ-SLC7A5,也称为hsa_circ_0040796)是否与ESCC的发病机制存在因果关系。

方法

通过qRT-PCR或免疫印迹法检测circ-SLC7A5、微小RNA(miR)-874-3p和冠蛋白-1C(CORO1C)的表达水平。通过集落形成、EdU、流式细胞术、Transwell和伤口愈合试验检测细胞功能表型。应用RNA免疫沉淀(RIP)和双荧光素酶报告基因试验确定circ-SLC7A5/miR-874-3p和miR-874-3p/CORO1C之间的关系。

结果

circ-SLC7A5在人ESCC中高表达。circ-SLC7A5缺失会损害细胞生长、迁移、侵袭能力,并促进细胞凋亡。circ-SLC7A5敲低会降低ESCC细胞的致瘤性。机制上,circ-SLC7A5包含一个与miR-874-3p的结合位点。此外,miR-874-3p负责circ-SLC7A5在ESCC细胞中的功能。CORO1C是miR-874-3p的直接靶标。circ-SLC7A5作为竞争性内源RNA(ceRNA),通过竞争共享的miR-874-3p来调控CORO1C。此外,CORO1C敲低在影响ESCC细胞生物学行为方面模拟了miR-874-3p过表达的效果。

结论

这些发现确定circ-SLC7A5是ESCC细胞的关键调节因子,并在ESCC中建立了一个新的circ-SLC7A5/miR-874-3p/CORO1C ceRNA网络。

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