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一种新型长链非编码RNA AC112721.1通过直接结合THBS1并调节miR-491-5p/C2CD2L轴促进三阴性乳腺癌的进展。

A novel lncRNA AC112721.1 promotes the progression of triple-negative breast cancer by directly binding to THBS1 and regulating miR-491-5p/C2CD2L axis.

作者信息

Ma Ping, Kang Shiyao, Li Huimin, Li Ming, Zhao Yuan, Yuan Hongjun, Pang Jianyu, Tang Wenru, Sheng Miaomiao

机构信息

Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming, 650500, Yunnan, China.

Department of Oncology, Puer People's Hospital, Puer, 665000, Yunnan, China.

出版信息

Sci Rep. 2024 Dec 30;14(1):32056. doi: 10.1038/s41598-024-83665-0.

Abstract

Triple-negative breast cancer (TNBC) seriously threatens women's health, and long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play fundamental roles in TNBC. This study aimed to identify lncRNAs that represent effective targets for the early diagnosis or treatment of TNBC. Here, we utilized the TCGA database to analyze differentially expressed genes, and survival analysis and ROC curve analysis were also performed. Notably, we identified a novel lncRNA, AC112721.1, that is significantly overexpressed in TNBC and is associated with poor overall survival in TNBC patients. Loss- and gain-of-function experiments revealed that AC112721.1 significantly promoted cell proliferation and migration, suppressed cell apoptosis in vitro and inhibited tumorigenesis in vivo. Further study of the mechanisms underlying these effects revealed that AC112721.1 regulates the Ras pathway by directly binding to THBS1 protein and functions as a ceRNA by sponging miR-491-5p to increase the expression of C2CD2L, thereby influencing the progression of TNBC. Our findings indicate that AC112721.1 may represent a new biomarker for evaluating TNBC prognosis and treating TNBC.

摘要

三阴性乳腺癌(TNBC)严重威胁女性健康,长链非编码RNA(lncRNAs)正成为基因表达的关键调节因子,并在TNBC中发挥重要作用。本研究旨在鉴定可作为TNBC早期诊断或治疗有效靶点的lncRNAs。在此,我们利用TCGA数据库分析差异表达基因,并进行了生存分析和ROC曲线分析。值得注意的是,我们鉴定出一种新型lncRNA,即AC112721.1,其在TNBC中显著高表达,且与TNBC患者的总生存期较差相关。功能缺失和功能获得实验表明,AC112721.1在体外显著促进细胞增殖和迁移、抑制细胞凋亡,并在体内抑制肿瘤发生。对这些作用潜在机制的进一步研究表明,AC112721.1通过直接结合THBS1蛋白来调节Ras通路,并通过海绵吸附miR-491-5p作为竞争性内源RNA(ceRNA)来增加C2CD2L的表达,从而影响TNBC的进展。我们的研究结果表明,AC112721.1可能是评估TNBC预后和治疗TNBC的一种新生物标志物。

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