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ARNT2的泛癌分析及其在宫颈癌中的致癌作用。

Pan-cancer analysis of ARNT2 and its oncogenic role in cervical cancer.

作者信息

Jin Dongdong, Wang Nannan, Xue Yang, Yang Yan, Shi Kaige, Wu He, Sheu Jim Jinn-Chyuan, Jeong Ji-Hak, Ban Zhenying, Shen Dandan, Yang Li

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

J Gynecol Oncol. 2025 May 26. doi: 10.3802/jgo.2025.36.e113.

Abstract

OBJECTIVE

This study aims to elucidate the role of aryl hydrocarbon receptor nuclear transporter 2 (ARNT2) in cervical cancer (CC) and explore the potential mechanism by which ARNT2 promotes the progression of CC through the protein phosphatase 2A (PP2A)/Akt signaling pathway.

METHODS

Bioinformatics tools were used to analyze the expression level of ARNT2 in cancer and its correlation with cancer prognosis. Western Blot and immunohistochemistry staining were used to detect the expression of ARNT2 protein in CC tissues and cells. ARNT2 was knocked down in SiHa and HeLa cells, respectively. Cell Counting Kit-8 assay and colony formation assay were used to detect changes in cell proliferation. Transwell assay and plate scratch assay were used to detect changes in cell migration and invasion. Western Blot assay was used to detect changes in the expression of PP2A/Akt signaling pathway after ARNT2 expression was downregulated. Finally, a CC xenograft tumor model was constructed to evaluate the effect of ARNT2 on SiHa cell tumorigenesis in vivo.

RESULTS

ARNT2 is highly expressed in tumor tissues and cell lines. ARNT2 knockdown can significantly inhibit the proliferation, invasion and migration of SiHa and HeLa cells in vitro and in xenograft models. Further studies have shown that ARNT2 may promote tumor formation by regulating the PP2A/Akt pathway.

CONCLUSION

ARNT2 promotes the malignant biological behavior of CC cells through the PP2A/Akt signaling pathway, confirming its potential as a prognostic marker for CC.

摘要

目的

本研究旨在阐明芳烃受体核转运蛋白2(ARNT2)在宫颈癌(CC)中的作用,并探讨ARNT2通过蛋白磷酸酶2A(PP2A)/Akt信号通路促进CC进展的潜在机制。

方法

利用生物信息学工具分析ARNT2在癌症中的表达水平及其与癌症预后的相关性。采用蛋白质免疫印迹法和免疫组织化学染色法检测CC组织和细胞中ARNT2蛋白的表达。分别在SiHa和HeLa细胞中敲低ARNT2。采用细胞计数试剂盒-8法和集落形成试验检测细胞增殖的变化。采用Transwell试验和平板划痕试验检测细胞迁移和侵袭的变化。采用蛋白质免疫印迹法检测下调ARNT2表达后PP2A/Akt信号通路表达的变化。最后,构建CC异种移植瘤模型,评估ARNT2对SiHa细胞体内成瘤的影响。

结果

ARNT2在肿瘤组织和细胞系中高表达。敲低ARNT2可显著抑制SiHa和HeLa细胞在体外和异种移植模型中的增殖、侵袭和迁移。进一步研究表明,ARNT2可能通过调节PP2A/Akt通路促进肿瘤形成。

结论

ARNT2通过PP2A/Akt信号通路促进CC细胞的恶性生物学行为,证实其作为CC预后标志物的潜力。

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