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miRNA-10a-5p的上调通过抑制UBE2I信号传导促进宫颈癌的肿瘤进展。

Upregulation of miRNA-10a-5p promotes tumor progression in cervical cancer by suppressing UBE2I signaling.

作者信息

Gu Yannan, Feng Xiaodan, Jin Yanqi, Liu Yuanlin, Zeng Li, Zhou Dachun, Feng Yuling

机构信息

Department of Obstetrics and Gynecology, Affiliated Maternal and Child Health Hospital of Nantong University, Nantong, China.

出版信息

J Obstet Gynaecol. 2023 Dec;43(1):2171283. doi: 10.1080/01443615.2023.2171283.

Abstract

Cervical cancer (CC) is a common malignant neoplasm in gynecology. There is increasing evidence to suggest that microRNAs (miRNAs) act as crucial regulators of CC. However, whether miR-10a-5p plays a role in CC is under investigation. The aim of this stuy was to assess the miR-10a-5p expression pattern in the development of CC and investigate its downstream target. MiR-10a-5p inhibition decreased CC cell proliferation and impaired CC cell invasion and migration but enhanced apoptosis. UBE2I was a direct target of miR-10a-5p. QRT-PCR results showed a down-regulation of UBE2I in CC cells, opposing miR-10a-5p. Besides, overexpression of miR-10a-5p down-regulated UBE2I. Functional rescue experiments further indicated the miR-10a-5p-UBE2I axis was linked to CC cell growth, apoptosis and metastasis. MiR-10a-5p upregulation promotes cervical cancer development by inhibiting UBE2I. These results also predict that miR-10a-5p may be a potential target for the clinical treatment of CC.IMPACT STATEMENT As a widely researched cancer-related miRNA, the overexpression of miR-10a-5p has been verified in various cancers. It has been described in a meta-analysis report that there were 42 miRNAs up-regulated and 21 miRNAs down-regulated in different stages of cervical cancer tissue versus healthy tissue. We verified that miR-10a-5p initiates and promotes tumor cell development by decreasing UBE2I abundance. This miR-10a-5p-mediated post-transcriptional regulation of UBE2I is involved in the tumorigenesis, invasion and migration of human cervical cancer. These findings provide mechanistic insights into how miR-10a-5p regulates cervical cancer hyper-proliferation and metastasis, as well as a new target for clinical treatment. Nevertheless, whether miR-10a-5p/UBE2I axis can be regulated by non-invasive methods need further exploration, which will be the focus of our future research.

摘要

宫颈癌(CC)是妇科常见的恶性肿瘤。越来越多的证据表明,微小RNA(miRNA)是宫颈癌的关键调节因子。然而,miR-10a-5p是否在宫颈癌中发挥作用仍在研究中。本研究的目的是评估miR-10a-5p在宫颈癌发生发展中的表达模式,并研究其下游靶点。抑制miR-10a-5p可降低宫颈癌细胞增殖,削弱宫颈癌细胞的侵袭和迁移能力,但可增强细胞凋亡。泛素结合酶E2I(UBE2I)是miR-10a-5p的直接靶点。实时定量聚合酶链反应(QRT-PCR)结果显示,宫颈癌细胞中UBE2I表达下调,与miR-10a-5p表达相反。此外,miR-10a-5p过表达可下调UBE2I。功能挽救实验进一步表明,miR-10a-5p-UBE2I轴与宫颈癌细胞的生长、凋亡和转移有关。miR-10a-5p上调通过抑制UBE2I促进宫颈癌发展。这些结果还预示,miR-10a-5p可能是宫颈癌临床治疗的潜在靶点。影响声明作为一种被广泛研究的癌症相关miRNA,miR-10a-5p的过表达已在多种癌症中得到证实。一项荟萃分析报告称,与健康组织相比,宫颈癌组织不同阶段有42种miRNA上调,21种miRNA下调。我们证实,miR-10a-5p通过降低UBE2I丰度启动并促进肿瘤细胞发展。这种miR-10a-5p介导的UBE2I转录后调控参与了人类宫颈癌的发生、侵袭和迁移。这些发现为miR-10a-5p如何调节宫颈癌过度增殖和转移提供了机制性见解,也为临床治疗提供了新靶点。然而,miR-10a-5p/UBE2I轴是否可通过非侵入性方法进行调控仍需进一步探索,这将是我们未来研究的重点。

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