ACOXL-AS1的泛癌动态及其对子宫内膜样癌的增殖影响。

IF 3.4 2区 医学 Q2 ONCOLOGY
Hongrong Wu, Ruilin Lin, Liangli Hong
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引用次数: 0

摘要

背景:长链非编码rna (lncRNAs)在癌变过程中起关键作用;然而,ACOXL-AS1的泛癌意义和功能机制在很大程度上仍不清楚。本研究全面探讨了ACOXL-AS1在多种恶性肿瘤中的表达格局、预后价值和生物学影响,并特别关注其在子宫内膜子宫内膜样癌(EEC)中的促增殖作用。方法:利用TCGA和GTEx数据库的泛癌RNA-seq数据分析ACOXL-AS1表达及其与临床结果的关系。通过慢病毒介导的过表达,在EEC细胞系(HHUA, hec - 1a)中进行功能验证,然后进行CCK-8,集落形成和跨井迁移/侵袭试验。使用综合生物信息学方法调查了机制见解。结果:ACOXL-AS1在大多数肿瘤中均显著下调,高表达与预后改善相关。升高的ACOXL-AS1水平与较小的肿瘤大小、较低的疾病分期、减少的转移和降低的肿瘤突变负担(TMB)/微卫星不稳定性(MSI)相关。它还能调节免疫抑制肿瘤微环境。关键是,在异种移植模型中,ACOXL-AS1过表达显著抑制EEC细胞的增殖、迁移、侵袭和肿瘤生长。在机制上,它可能通过同源重组途径在EEC细胞中调控RPA4的表达。结论:ACOXL-AS1可能在子宫内膜子宫内膜样癌(EEC)中发挥抑癌作用,提示其作为预后生物标志物的潜力和作为治疗靶点的候选物有待进一步探索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ACOXL-AS1's pan-cancer dynamics and its proliferative impact on endometrial endometrioid carcinoma.

Background: Long non-coding RNAs (lncRNAs) are critically involved in carcinogenesis; however, the pan-cancer significance and functional mechanisms of ACOXL-AS1 remain largely uncharacterized. This study comprehensively investigates the expression landscape, prognostic value, and biological impact of ACOXL-AS1 across multiple malignancies, with a specific focus on its pro-proliferative role in endometrial endometrioid carcinoma (EEC).

Methods: We analyzed ACOXL-AS1 expression and its association with clinical outcomes using pan-cancer RNA-seq data from TCGA and GTEx databases. Functional validation was performed in EEC cell lines (HHUA, HEC-1 A) via lentivirus-mediated overexpression, followed by CCK-8, colony formation, and transwell migration/invasion assays. Mechanistic insights were investigated using integrated bioinformatics approaches.

Results: ACOXL-AS1 was significantly downregulated in most cancers, and higher expression correlated with improved prognosis. Elevated ACOXL-AS1 levels were associated with smaller tumor size, lower disease stage, reduced metastasis, and decreased tumor mutational burden (TMB)/microsatellite instability (MSI). It also modulated the immunosuppressive tumor microenvironment. Critically, ACOXL-AS1 overexpression significantly inhibited EEC cell proliferation, migration, invasion, and tumor growth in xenograft models. Mechanistically, it may regulate RPA4 expression through the homologous recombination pathway in EEC cells.

Conclusions: ACOXL-AS1 may play a role as a tumor suppressor in endometrial endometrioid carcinoma (EEC), suggesting its potential as a prognostic biomarker and a candidate for further exploration as a therapeutic target.

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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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