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

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...

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Main Authors: Ping Ma, Shiyao Kang, Huimin Li, Ming Li, Yuan Zhao, Hongjun Yuan, Jianyu Pang, Wenru Tang, Miaomiao Sheng
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-83665-0
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author Ping Ma
Shiyao Kang
Huimin Li
Ming Li
Yuan Zhao
Hongjun Yuan
Jianyu Pang
Wenru Tang
Miaomiao Sheng
author_facet Ping Ma
Shiyao Kang
Huimin Li
Ming Li
Yuan Zhao
Hongjun Yuan
Jianyu Pang
Wenru Tang
Miaomiao Sheng
author_sort Ping Ma
collection DOAJ
description 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.
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institution Kabale University
issn 2045-2322
language English
publishDate 2024-12-01
publisher Nature Portfolio
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series Scientific Reports
spelling doaj-art-ec6edd2dc6aa4904ae31b838b6a1df5c2025-01-05T12:26:20ZengNature PortfolioScientific Reports2045-23222024-12-0114111410.1038/s41598-024-83665-0A novel lncRNA AC112721.1 promotes the progression of triple-negative breast cancer by directly binding to THBS1 and regulating miR-491-5p/C2CD2L axisPing Ma0Shiyao Kang1Huimin Li2Ming Li3Yuan Zhao4Hongjun Yuan5Jianyu Pang6Wenru Tang7Miaomiao Sheng8Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyDepartment of Oncology, Puer People’s HospitalLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyLaboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and TechnologyAbstract 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.https://doi.org/10.1038/s41598-024-83665-0Triple-negative breast cancerAC112721.1THBS1miR-491-5pC2CD2LProgression
spellingShingle Ping Ma
Shiyao Kang
Huimin Li
Ming Li
Yuan Zhao
Hongjun Yuan
Jianyu Pang
Wenru Tang
Miaomiao Sheng
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
Scientific Reports
Triple-negative breast cancer
AC112721.1
THBS1
miR-491-5p
C2CD2L
Progression
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort novel lncrna ac112721 1 promotes the progression of triple negative breast cancer by directly binding to thbs1 and regulating mir 491 5p c2cd2l axis
topic Triple-negative breast cancer
AC112721.1
THBS1
miR-491-5p
C2CD2L
Progression
url https://doi.org/10.1038/s41598-024-83665-0
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