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环状 RNA ZNF609 通过竞争性结合 microRNA-197-3p 作为竞争内源性 RNA 调节 E2F 转录因子 6,从而促进宫颈癌的进展。

Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression.

机构信息

Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.

Department of Gynecology and Obstetrics, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University), Suzhou, P.R. China.

出版信息

Bioengineered. 2021 Dec;12(1):927-936. doi: 10.1080/21655979.2021.1896116.

Abstract

Countless studies have demonstrated that Circular RNAs (circRNAs) exert vital effects in regulating tumorigenesis of various cancers. CircRNA ZNF609 (circ-ZNF609) has been reported as an oncogene in various human cancers. Nevertheless, its regulating effect in cervical cancer (CC) remains to be further explored. RT-qPCR was adopted to measure circ-ZNF609, miR-197-3p and E2F6 levels. CC cell proliferation, migration and invasion were analyzed via CCK-8 and transwell assays. Dual-luciferase reporter assay was adopted to confirm the interaction between miR-197-3p and circ-ZNF609 or E2F6. In the present study, it was found that circ-ZNF609 was elevated in CC tissues and cell lines, and circ-ZNF609 deletion repressed cell viability, migration and invasion in CC. Moreover, circ-ZNF609 was identified to negatively regulate miR-197-3p expression in CC cells. The inhibition of miR-197-3p abrogated the inhibitory effect on CC cell proliferation, migration and invasion induced by circ-ZNF609 knockdown. Additionally, we further demonstrated that circ-ZNF609 upregulated E2F6 by interacting with miR-197-3p. Finally, rescue assays indicated that E2F6 overexpression upended the suppression of CC progression induced by circ-ZNF609 deletion. In conclusion, circ-ZNF609 promoted CC progression through modulating the miR-197-3p/E2F6 axis as an oncogene. This finding offers a unique insight into CC molecular mechanism and suggests a potential target for CC therapy.

摘要

无数研究表明,环状 RNA(circRNA)在调节各种癌症的肿瘤发生中发挥着重要作用。环状 RNA ZNF609(circ-ZNF609)已被报道为多种人类癌症的癌基因。然而,其在宫颈癌(CC)中的调节作用仍有待进一步探讨。采用 RT-qPCR 测量 circ-ZNF609、miR-197-3p 和 E2F6 水平。通过 CCK-8 和 Transwell 测定分析 CC 细胞增殖、迁移和侵袭。采用双荧光素酶报告基因实验证实 miR-197-3p 与 circ-ZNF609 或 E2F6 的相互作用。在本研究中,发现 circ-ZNF609 在 CC 组织和细胞系中升高,circ-ZNF609 缺失抑制 CC 细胞活力、迁移和侵袭。此外,circ-ZNF609 被鉴定为负调控 CC 细胞中 miR-197-3p 的表达。抑制 miR-197-3p 可消除 circ-ZNF609 敲低对 CC 细胞增殖、迁移和侵袭的抑制作用。此外,我们进一步证明 circ-ZNF609 通过与 miR-197-3p 相互作用而上调 E2F6。最后,挽救实验表明,E2F6 过表达推翻了 circ-ZNF609 缺失对 CC 进展的抑制作用。总之,circ-ZNF609 通过调节 miR-197-3p/E2F6 轴作为癌基因促进 CC 进展。这一发现为 CC 的分子机制提供了独特的见解,并为 CC 的治疗提供了一个潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce0/8291891/7557d067e8dd/KBIE_A_1896116_UF0001_OC.jpg

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