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长链非编码RNA ADAMTS9-AS1通过miR-575/CADM2调控食管癌细胞的增殖、迁移和侵袭。

LncRNA ADAMTS9-AS1 regulates the proliferation, migration, and invasion of esophageal cancer cells via miR-575/ CADM2.

作者信息

Wang Jinhua, Ji Wei, Qu Hongxia, Sun Yingying, Zhang Tiesong

机构信息

Department of Gastroenterology, Xiangzhou District People's Hospital of Xiangyang, Xiangyang, 441100, China.

Beijing Institute of Biotechnology, Beijing, 100071, China.

出版信息

Discov Oncol. 2025 Aug 31;16(1):1660. doi: 10.1007/s12672-025-03248-x.

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) ranks among the most lethal malignant neoplasms globally, representing a significant risk to public health.

OBJECTIVES

This study investigates the impact of lncRNA ADAMTS9-AS1 on the function of ESCC cells by targeting and regulating miR-575/CADM2 axis.

MATERIALS AND METHODS

qPCR was employed to assess the expression of ADAMTS9-AS1, miR-575, and CADM2 in ESCC tissues and cells. Chi-square test was utilized to examine the association between ADAMTS9-AS1 and clinical indicators. Cox model was applied to identify risk factors of poor prognosis, and survival curves were generated using the Kaplan-Meier method. Furthermore, the effects of overexpressing ADAMTS9-AS1 alone and in conjunction with miR-575 were analyzed in ESCC cell lines, utilizing CCK-8 assays to evaluate cell proliferation, and Transwell assays to assess cell invasion and migration capabilities.

RESULTS

The study revealed that in ESCC tissues and cell lines, the expression levels of ADAMTS9-AS1 and CADM2 were decreased and exhibited a positive correlation, whereas the miR-575 was elevated and demonstrated a negative correlation with both molecules. The expression of ADAMTS9-AS1 was associated with TNM staging and lymph node metastasis, serving as a risk factor for poor prognosis. Overexpression ADAMTS9-AS1 could inhibit miR-575 expression, and suppress cellular proliferation, migration, and invasion. However, this inhibitory effect was reversed when miR-575 was concurrently overexpressed.

CONCLUSION

The targeting effect of ADAMTS9-AS1 on miR-575/CADM2 changes in ESCC cell function and further mediated the progression of ESCC. ADAMTS9-AS1 has the potential to be a prognostic biomarker and molecular target for ESCC.

摘要

背景

食管鳞状细胞癌(ESCC)是全球致死率最高的恶性肿瘤之一,对公众健康构成重大威胁。

目的

本研究旨在通过靶向调控miR-575/CADM2轴,探讨lncRNA ADAMTS9-AS1对ESCC细胞功能的影响。

材料与方法

采用qPCR检测ESCC组织及细胞中ADAMTS9-AS1、miR-575和CADM2的表达。运用卡方检验分析ADAMTS9-AS1与临床指标的相关性。应用Cox模型识别预后不良的危险因素,并采用Kaplan-Meier法绘制生存曲线。此外,在ESCC细胞系中分析单独过表达ADAMTS9-AS1以及与miR-575联合过表达的效果,利用CCK-8法评估细胞增殖,采用Transwell法评估细胞侵袭和迁移能力。

结果

研究发现,在ESCC组织和细胞系中,ADAMTS9-AS1和CADM2的表达水平降低且呈正相关,而miR-575表达升高且与这两个分子均呈负相关。ADAMTS9-AS1的表达与TNM分期和淋巴结转移相关,是预后不良的危险因素。过表达ADAMTS9-AS1可抑制miR-575表达,并抑制细胞增殖、迁移和侵袭。然而,当同时过表达miR-575时,这种抑制作用被逆转。

结论

ADAMTS9-AS1对miR-575/CADM2的靶向作用改变了ESCC细胞功能,并进一步介导了ESCC的进展。ADAMTS9-AS1有可能成为ESCC的预后生物标志物和分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a833/12399493/69b641c3c675/12672_2025_3248_Fig1_HTML.jpg

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