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Updated: Jan 18, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
lncRNA-miRNA/RBP-mRNA Network Involved in Human Triple-Negative Breast Cancer: An Integrated Approach
Wen Yun1, Yao Li2, Jianyuan Huang3
1Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China.
Abstract:
Noncoding RNA regulatory networks play crucial roles in human breast cancer. The aim of this study was to establish a network containing multi-type RNAs and RBPs in triple-negative breast cancer (TNBC). Differential expression analyses of lncRNAs, miRNAs, and genes were performed using the GEO2R tool. Downstream RBPs and miRNAs were identified using respective databases. GO, KEGG, and protein-protein interaction were predicted. Expression of mRNAs, lncRNAs, and miRNAs were examined using TCGA and ENCORI. TMEM161B-AS1-miR-3646-SERPINB5 axis was validated with the expression level and cell function. TMEM161B-AS1-RBFOX1-SER-PINB5 axis was validated using RIP assays. A lncRNA-miRNA-mRNA network, a lncRNA-RBP-mRNA network, and a lncRNA-miRNA/RBP-mRNA network were constructed. Alterations in the expression levels of TMEM161B-AS1, miR-3646, and SERPINB5 were confirmed by real-time polymerase chain reaction as downregulation, upregulation, and downregulation, respectively. TMEM161B-AS1 inhibited TNBC cell proliferation, migration, and invasion. miR-3646 reversed the inhibitory effect of TMEM161B-AS1 on cell function, while SERPINB5 offset the miR-3646 effect. RB-FOX1 bound to SERPINB5 mRNAs, and TMEM161B-AS1 was involved in their interaction. This study revealed the ln-cRNA-miRNA/RBP-mRNA network in TNBC, providing more directions to study the molecular mechanism of TNBC.
Insights
This study reveals a novel RNA regulatory network in triple-negative breast cancer (TNBC). The TMEM161B-AS1-miR-3646-SERPINB5 axis impacts TNBC cell functions, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Noncoding RNAs are critical in human breast cancer.
- Triple-negative breast cancer (TNBC) requires further understanding of its molecular mechanisms.
Purpose of the Study:
- To construct a comprehensive regulatory network involving multi-type RNAs and RNA-binding proteins (RBPs) in TNBC.
- To identify key molecular players and their interactions within this network.
Main Methods:
- Differential expression analysis of lncRNAs, miRNAs, and genes using GEO2R.
- Identification of downstream RBPs and miRNAs via databases.
- Network construction including lncRNA-miRNA-mRNA and lncRNA-RBP-mRNA interactions.
- Validation using TCGA, ENCORI, real-time PCR, and RIP assays.
Main Results:
- A novel TMEM161B-AS1-miR-3646-SERPINB5 axis was identified, affecting TNBC cell proliferation, migration, and invasion.
- TMEM161B-AS1 demonstrated inhibitory effects, miR-3646 reversed these effects, and SERPINB5 counteracted miR-3646.
- RBFOX1 was found to bind SERPINB5 mRNAs, with TMEM161B-AS1 influencing this interaction.
Conclusions:
- The study established a multi-type RNA and RBP network in TNBC.
- The identified TMEM161B-AS1-miR-3646-SERPINB5 axis and TMEM161B-AS1-RBFOX1-SERPINB5 axis provide insights into TNBC pathogenesis.
- These findings offer potential directions for future TNBC research and therapeutic strategies.
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