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Hsa_circ_0072008 通过 miR-1305/解旋酶、淋巴特异性(HELLS)轴调控宫颈鳞状细胞癌中的细胞增殖、迁移和侵袭。

Hsa_circ_0072008 regulates cell proliferation, migration, and invasion in cervical squamous cell carcinoma via miR-1305/helicase, lymphoid specific (HELLS) axis.

机构信息

Department of Gynecology, Jingmen NO. 1 People's Hospital, Jingmen, Hubei, China.

出版信息

Bioengineered. 2022 Apr;13(4):8311-8322. doi: 10.1080/21655979.2022.2048945.

Abstract

Cervical squamous cell carcinoma (CESC) is one of the most common cancers in women. Recent studies have proved that circular RNAs (circRNAs) could regulate the progress of CESC, but the mechanism is still indistinct. In this work, we explored the roles of circ_0072008 in CESC. The expression levels of circ_0072008, microRNA-1305 (miR-1305) and mRNA of HELLS (helicase, lymphoid specific) were detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in CESC tissues. Meanwhile, the level of HELLS was quantified by western blot analysis. Besides, the cell functions were examined by colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay, flow cytometry assay and western blot. Furthermore, the interaction between miR-1305 and circ_0072008 or HELLS was detected by dual-luciferase reporter assay. The function of circ_0072008 in CESC has also been further verified by xenograft model experiments. The levels of circ_0072008 and HELLS were upregulated, and the miR-1305 level was decreased in CESC tissues in contrast to that in normal tissues. For functional analysis, silencing circ_0072008 inhibited cell proliferation and cell migration, whereas enhanced cell apoptosis in CESC cells. In mechanism, circ_0072008 acted as a miR-1305 sponge to regulate the level of HELLS. Moreover, miR-1305 was confirmed to repress the progression of CESC cells by suppressing HELLS. Meanwhile, knockdown of circ_0072008 inhibited CESC cells growth . In conclusion, circ_0072008 facilitated CESC cell proliferation, migration, and invasion through increasing HELLS expression by regulating miR-1305, which also offered an underlying targeted therapy for CESC treatment.

摘要

宫颈鳞状细胞癌(CESC)是女性最常见的癌症之一。最近的研究已经证明,环状 RNA(circRNA)可以调节 CESC 的进展,但机制尚不清楚。在这项工作中,我们探讨了 circ_0072008 在 CESC 中的作用。通过实时定量逆转录聚合酶链反应(qRT-PCR)检测 CESC 组织中 circ_0072008、microRNA-1305(miR-1305)和 HELLS(核酸酶,淋巴特异性)mRNA 的表达水平。同时,通过 Western blot 分析定量 HELLS 的水平。此外,通过集落形成试验、5-乙炔基-2'-脱氧尿苷(EdU)试验、划痕愈合试验、流式细胞术分析和 Western blot 检测细胞功能。此外,通过双荧光素酶报告基因检测法检测 miR-1305 与 circ_0072008 或 HELLS 的相互作用。通过异种移植模型实验进一步验证了 circ_0072008 在 CESC 中的作用。与正常组织相比,CESC 组织中 circ_0072008 和 HELLS 的水平上调,而 miR-1305 的水平下调。功能分析显示,沉默 circ_0072008 抑制 CESC 细胞的增殖和迁移,而促进细胞凋亡。在机制上,circ_0072008 作为 miR-1305 的海绵体调节 HELLS 的水平。此外,miR-1305 通过抑制 HELLS 来抑制 CESC 细胞的进展。同时,circ_0072008 的敲低抑制了 CESC 细胞的生长。总之,circ_0072008 通过调节 miR-1305 增加 HELLS 的表达,促进 CESC 细胞的增殖、迁移和侵袭,为 CESC 的治疗提供了潜在的靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/9161871/c4f6ab71090e/KBIE_A_2048945_UF0001_OC.jpg

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