ZC3H13-induced the m6A modification of hsa_circ_0081723 promotes cervical cancer progression via AMPK/p53 pathway.

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Journal of Obstetrics and Gynaecology Research Pub Date : 2024-10-30 DOI:10.1111/jog.16140
Qiong Wei, Yi Yang, Chun Li, Huimin Wang
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Abstract

Background: N6-methyladenosine (m6A) modification and circular RNAs (circRNAs) have been confirmed to participate in cervical cancer (CC) progression. However, the function of a novel circRNA, hsa_circ_0081723, has not yet been explored in CC. Therefore, this study aimed to investigate the potential role of hsa_circ_0081723 and its m6A modification in CC.

Methods: The hsa_circ_0081723 and ZC3H13 expressions were examined by qRT-PCR in the CC tissues, and their prognostic significance was evaluated via Kaplan-Meier Plotter. The role of hsa_circ_0081723 in CC progression was checked by loss-of-function assays. The relative protein levels of AMPK/p53 pathway were determined by western blotting. The interactions of hsa_circ_0081723 and ZC3H13 were verified via MeRIP and RNA stability assays.

Results: The hsa_circ_0081723 expression was elevated in CC samples, and its higher levels indicated high histological grade, high FIGO stage, poor differentiation, and poor prognosis. Functionally, silencing hsa_circ_0081723 impaired the malignant behavior of CC cells and enhanced the protein levels of key molecules of the AMPK signaling pathway. Moreover, ZC3H13 was also elevated in CC samples and demonstrated a positive association with hsa_circ_0081723. The relative enrichment of hsa_circ_0081723 m6A and its stability were enhanced in ZC3H13 overexpressed CC cells. Mechanically, ZC3H13 overexpression partially reversed the antitumor effects caused by hsa_circ_0081723 knockdown in CC cells.

Conclusions: This study innovatively demonstrates that ZC3H13-mediated m6A modification of hsa_circ_0081723 promotes CC progression by modulating AMPK/p53 pathway. Our findings may contribute to the understanding of the molecular mechanisms underlying CC and offer potential therapeutic targets for clinical treatment.

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ZC3H13诱导的hsa_circ_0081723的m6A修饰通过AMPK/p53途径促进宫颈癌的进展。
背景:N6-甲基腺苷(m6A)修饰和环状 RNA(circRNA)已被证实参与宫颈癌(CC)的进展。然而,一种新的环状 RNA(hsa_circ_0081723)在宫颈癌中的功能尚未得到探讨。因此,本研究旨在探讨 hsa_circ_0081723 及其 m6A 修饰在 CC 中的潜在作用:方法:通过qRT-PCR检测hsa_circ_0081723和ZC3H13在CC组织中的表达,并通过Kaplan-Meier Plotter评估其预后意义。通过功能缺失实验检测了hsa_circ_0081723在CC进展中的作用。蛋白印迹法测定了AMPK/p53通路的相对蛋白水平。通过MeRIP和RNA稳定性实验验证了hsa_circ_0081723与ZC3H13的相互作用:结果:hsa_circ_0081723在CC样本中表达升高,其较高水平表明组织学分级高、FIGO分期高、分化差和预后差。从功能上讲,沉默hsa_circ_0081723可抑制CC细胞的恶性行为,并提高AMPK信号通路关键分子的蛋白水平。此外,ZC3H13也在CC样本中升高,并与hsa_circ_0081723呈正相关。在ZC3H13过表达的CC细胞中,hsa_circ_0081723 m6A的相对富集度和稳定性都有所提高。从机理上讲,ZC3H13的过表达部分逆转了敲除hsa_circ_0081723对CC细胞的抗肿瘤作用:本研究创新性地证明了 ZC3H13 介导的 hsa_circ_0081723 m6A 修饰通过调节 AMPK/p53 通路促进了 CC 的进展。我们的研究结果可能有助于理解CC的分子机制,并为临床治疗提供潜在的治疗靶点。
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来源期刊
CiteScore
3.10
自引率
0.00%
发文量
376
审稿时长
3-6 weeks
期刊介绍: The Journal of Obstetrics and Gynaecology Research is the official Journal of the Asia and Oceania Federation of Obstetrics and Gynecology and of the Japan Society of Obstetrics and Gynecology, and aims to provide a medium for the publication of articles in the fields of obstetrics and gynecology. The Journal publishes original research articles, case reports, review articles and letters to the editor. The Journal will give publication priority to original research articles over case reports. Accepted papers become the exclusive licence of the Journal. Manuscripts are peer reviewed by at least two referees and/or Associate Editors expert in the field of the submitted paper.
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