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HOXD Antisense Growth-Associated Long Noncoding RNA Promotes Triple-Negative Breast Cancer Progression by Activating
Chenguang Zhang1, Ying Yang2, Lina Yi3
1Department of Breast Surgery, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Purpose:
Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options, which has a substantial deleterious effect on patients' lives. HOXD antisense growth-associated long noncoding RNA (lncRNA) (HAGLR) plays tumor-promoting roles in many cancers. In this study, we aimed to explore the role of HAGLR in TNBC.
Methods:
Quantitative real-time polymerase chain reaction assays were used to examine the expression of RNAs. Functional experiments were conducted to test the biological behavior of TNBC cells. Moreover, MS2-RNA immunoprecipitation, luciferase reporter, and RNA pull-down assays were conducted to verify the binding relationship between HAGLR, microRNA-143-5p (miR-143-5p), and serine- and arginine-rich splicing factor 1 (SRSF1).
Results:
HAGLR was found to be highly expressed in TNBC tissues and cells, and inhibiting HAGLR suppressed cell proliferation, migration, and invasion and promoted cell apoptosis in TNBC. Meanwhile, miR-93-5p was shown to bind to HAGLR and SRSF1. In addition, SRSF1 plays an oncogenic role in TNBC. Importantly, HAGLR could activate the Wnt signaling pathway by sponging miR-93-5p to upregulate SRSF1; thus, accelerating TNBC progression.
Conclusion:
HAGLR could promote the progression of TNBC through the miR-93-5p/SRSF1 axis to activate the Wnt signaling pathway.
Insights
HOXD antisense growth-associated long noncoding RNA (HAGLR) promotes triple-negative breast cancer (TNBC) progression by activating the Wnt pathway. Inhibiting HAGLR suppressed TNBC cell growth and invasion, offering a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- HOXD antisense growth-associated long noncoding RNA (HAGLR) has been implicated in various cancers.
Purpose of the Study:
- To investigate the role and mechanism of HAGLR in triple-negative breast cancer (TNBC).
- To explore the potential of HAGLR as a therapeutic target for TNBC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) for RNA expression analysis.
- In vitro functional assays to assess TNBC cell proliferation, migration, invasion, and apoptosis.
- Molecular assays including MS2-RNA immunoprecipitation, luciferase reporter assays, and RNA pull-down assays to determine molecular interactions.
Main Results:
- HAGLR expression is significantly upregulated in TNBC tissues and cells.
- Inhibition of HAGLR suppresses TNBC cell proliferation, migration, and invasion, while promoting apoptosis.
- HAGLR acts as a molecular sponge for miR-93-5p, leading to the upregulation of serine- and arginine-rich splicing factor 1 (SRSF1).
- The HAGLR/miR-93-5p/SRSF1 axis activates the Wnt signaling pathway, thereby promoting TNBC progression.
Conclusions:
- HAGLR promotes TNBC progression via the miR-93-5p/SRSF1 axis by activating the Wnt signaling pathway.
- Targeting HAGLR represents a potential therapeutic strategy for triple-negative breast cancer.
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