Inhibiting SNX10 induces autophagy to suppress invasion and EMT and inhibits the PI3K/AKT pathway in cervical cancer.

IF 2.8 3区 医学 Q2 ONCOLOGY Clinical & Translational Oncology Pub Date : 2024-10-05 DOI:10.1007/s12094-024-03715-x
Dan Liao, Yanxian He, Bin He, Saitian Zeng, Yejia Cui, Cuifen Li, Haohai Huang
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Abstract

Purpose: Cervical cancer (CC) is a prevalent malignancy among women with high morbidity and poor prognosis. Sorting nexin 10 (SNX10) is a newly recognized cancer regulatory factor, while its action on CC progression remains elusive. Hence, this study studied the effect of SNX10 on CC development and investigated the mechanism.

Methods: The SNX10 level in CC and the overall survival of CC cases with different SNX10 expressions were determined by bioinformatics analysis in GEPIA. The SNX10 expression in tumor tissues and clinical significance were studied in 64 CC cases. The overall survival was assessed using Kaplan-Meier analysis. The formation of LC3 was evaluated using immunofluorescence. Cell invasion was measured using the Transwell assay. Epithelial-to-mesenchymal transition (EMT) was determined by observing cell morphology and assessing EMT marker levels. A xenograft tumor was constructed to evaluate tumor growth.

Results: SNX10 was elevated in CC tissues and cells, and the CC cases with high SNX10 levels exhibited poor overall survival. Besides, SNX10 correlated with the FIGO stage, lymph node invasion, and stromal invasion of CC. SNX10 silencing induced CC cell autophagy and suppressed CC cell invasion and EMT. Meanwhile, silenced SNX10 could suppress invasion and EMT via inducing autophagy. Furthermore, SNX10 inhibition suppressed the PI3K/AKT pathway. Moreover, silenced SNX10 restrained the tumor growth, autophagy, and EMT of CC in vivo.

Conclusion: SNX10 was enhanced in CC and correlated with poor prognosis. Silenced SNX10 induced autophagy to suppress invasion and EMT and inhibited the PI3K/AKT pathway in CC, making SNX10 a valuable molecule for CC therapy.

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抑制 SNX10 可诱导自噬,从而抑制宫颈癌的侵袭和 EMT,并抑制 PI3K/AKT 通路。
目的:宫颈癌(CC)是妇女中一种发病率高、预后差的常见恶性肿瘤。Sorting nexin 10(SNX10)是一种新近被确认的癌症调控因子,但其对宫颈癌进展的作用仍不明确。因此,本研究探讨了SNX10对CC发展的影响并研究了其机制:方法:通过GEPIA中的生物信息学分析,确定SNX10在CC中的水平以及不同SNX10表达的CC病例的总生存率。研究了64例CC患者肿瘤组织中SNX10的表达情况及其临床意义。采用 Kaplan-Meier 分析法评估总生存率。使用免疫荧光评估 LC3 的形成。细胞侵袭采用 Transwell 试验进行测量。上皮细胞向间质转化(EMT)是通过观察细胞形态和评估EMT标记物水平来确定的。构建异种移植瘤以评估肿瘤生长情况:结果:SNX10在CC组织和细胞中升高,SNX10水平高的CC病例总生存率低。此外,SNX10还与CC的FIGO分期、淋巴结侵犯和基质侵犯相关。沉默SNX10可诱导CC细胞自噬,抑制CC细胞侵袭和EMT。同时,沉默的SNX10可通过诱导自噬抑制侵袭和EMT。此外,抑制SNX10还能抑制PI3K/AKT通路。此外,沉默的SNX10抑制了CC体内的肿瘤生长、自噬和EMT:结论:SNX10在CC中增强,并与不良预后相关。沉默的SNX10可诱导自噬以抑制CC的侵袭和EMT,并抑制PI3K/AKT通路,从而使SNX10成为治疗CC的重要分子。
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来源期刊
CiteScore
6.20
自引率
2.90%
发文量
240
审稿时长
1 months
期刊介绍: Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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