Department of Obstetrics and Gynecology, Wuhan Third Hospital, Wuhan, Hubei, China.
J Obstet Gynaecol Res. 2024 Dec;50(12):2286-2298. doi: 10.1111/jog.16140. Epub 2024 Oct 30.
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.
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.
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.
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.
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，一种新型 circRNA，hsa_circ_0081723，在 CC 中的功能尚未被探索。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。
通过 qRT-PCR 检测 CC 组织中 hsa_circ_0081723 和 ZC3H13 的表达，并通过 Kaplan-Meier Plotter 评估其预后意义。通过功能丧失实验检测 hsa_circ_0081723 在 CC 进展中的作用。通过 Western blot 检测 AMPK/p53 通路的相对蛋白水平。通过 MeRIP 和 RNA 稳定性实验验证 hsa_circ_0081723 和 ZC3H13 的相互作用。
hsa_circ_0081723 在 CC 样本中表达上调，其高水平提示组织学分级高、FIGO 分期高、分化差、预后差。功能上，沉默 hsa_circ_0081723 可抑制 CC 细胞的恶性行为，并增强 AMPK 信号通路关键分子的蛋白水平。此外，ZC3H13 在 CC 样本中也上调，并与 hsa_circ_0081723 呈正相关。ZC3H13 过表达的 CC 细胞中 hsa_circ_0081723 的相对 m6A 富集和稳定性增强。机制上，ZC3H13 过表达部分逆转了 hsa_circ_0081723 敲低在 CC 细胞中引起的抗肿瘤作用。
本研究创新性地表明，ZC3H13 介导的 hsa_circ_0081723 的 m6A 修饰通过调节 AMPK/p53 通路促进 CC 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。
