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微小RNA-641通过直接靶向……抑制宫颈癌细胞的增殖、迁移和侵袭并诱导其凋亡。

miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting .

作者信息

Yao Rui, Zheng Huzhong, Wu Liqun, Cai Pingsheng

机构信息

Department of Obstetrics and Gynecology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000, Zhejiang, People's Republic of China,

出版信息

Onco Targets Ther. 2018 Dec 11;11:8965-8976. doi: 10.2147/OTT.S190303. eCollection 2018.

Abstract

BACKGROUND

miRNAs have been found to be dysregulated in cervical cancer. The dysregulation of miRNA has been implicated in cervical carcinogenesis and progression. Therefore, further studies of the specific roles of deregulated miRNAs in cervical cancer and underlying molecular mechanisms may facilitate the identification of novel therapeutic techniques for patients with this disease. miRNA-641 (miR-641) was previously reported to serve an important role in lung cancer. However, the expression pattern and roles of miR-641 in cervical cancer remain unclear.

METHOD

In this study, the expression level of miR-641 in cervical cancer tissues and cell lines was detected using RT-qPCR. The influence of miR-641 upregulation in cervical cancer cell proliferation, apoptosis, migration and invasion was evaluated using CCK-8 assay, flow cytometry assay, migration and invasion assays, respectively. In vivo tumor growth assay was utilized to determine the effect of miR-641 overexpression in the tumor growth of cervical cancer cells in vivo. The molecular mechanisms underlying the action of miR-641 in cervical cancer cells were also explored.

RESULTS

We found that miR-641 expression was obviously decreased in cervical cancer tissues and cell lines, which strongly correlated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Upregulation of miR-641 inhibited cell proliferation, induced apoptosis, and reduced metastasis in cervical cancer. Additionally, bioinformatics analysis predicted as a novel target gene of miR-641. Notably, luciferase reporter assay, RT-qPCR, and Western blot analysis revealed that miR-641 decreased expression in cervical cancer cells by directly targeting its 3'-untranslated region. Furthermore, was upregulated in cervical cancer tissues, which was negatively correlated with miR-641 expression. Moreover, recovered ZEB1 expression attenuated the tumor suppressive action of miR-641 overexpression in the malignant phenotypes of cervical cancer cells. Besides, miR-641 could hinder cervical cancer tumor growth in vivo by inhibiting .

CONCLUSION

These results indicate that miR-641 has tumor suppressive roles in the development of cervical cancer by directly targeting , suggesting that miR-641 is a novel, effective therapeutic target for treating patients with this disease.

摘要

背景

已发现miRNA在宫颈癌中表达失调。miRNA的失调与宫颈癌的发生和发展有关。因此,进一步研究失调的miRNA在宫颈癌中的具体作用及其潜在分子机制,可能有助于为该疾病患者确定新的治疗技术。此前有报道称miRNA-641(miR-641)在肺癌中发挥重要作用。然而,miR-641在宫颈癌中的表达模式和作用仍不清楚。

方法

在本研究中,采用RT-qPCR检测miR-641在宫颈癌组织和细胞系中的表达水平。分别使用CCK-8法、流式细胞术、迁移和侵袭实验评估miR-641上调对宫颈癌细胞增殖、凋亡、迁移和侵袭的影响。利用体内肿瘤生长实验确定miR-641过表达对宫颈癌细胞体内肿瘤生长的影响。还探讨了miR-641在宫颈癌细胞中作用的分子机制。

结果

我们发现miR-在宫颈癌组织和细胞系中表达明显降低,这与国际妇产科联盟分期和淋巴结转移密切相关。miR-641上调可抑制宫颈癌细胞增殖、诱导凋亡并减少转移。此外,生物信息学分析预测 为miR-641的一个新靶基因。值得注意的是,荧光素酶报告基因实验、RT-qPCR和蛋白质免疫印迹分析表明,miR-641通过直接靶向其3'-非翻译区降低宫颈癌细胞中 的表达。此外, 在宫颈癌组织中上调,与miR-641表达呈负相关。而且,恢复ZEB1表达可减弱miR-641过表达对宫颈癌细胞恶性表型的肿瘤抑制作用。此外,miR-641可通过抑制 在体内阻碍宫颈癌肿瘤生长。

结论

这些结果表明,miR-641通过直接靶向 在宫颈癌发生发展中具有肿瘤抑制作用,提示miR-641是治疗该疾病患者的一个新的有效治疗靶点。

需注意,原文中部分基因名称未完整给出,翻译时保留了原文的格式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2736/6294066/325daa9bb812/ott-11-8965Fig1.jpg

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