J Breast Cancer.  2021 Jun;24(3):315-329. 10.4048/jbc.2021.24.e24.

HOXD Antisense Growth-Associated Long Noncoding RNA Promotes TripleNegative Breast Cancer Progression by Activating Wnt Signaling Pathway

• Zhang C
• Yang Y
• Yi L
• Paizula X
• Xu W
• Wu X

• KMID: 2517345
• DOI: http://doi.org/10.4048/jbc.2021.24.e24

Abstract

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 pulldown 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.

Keyword

RNA; long noncoding; MicroRNAs; Triple negative breast neoplasms; Wnt signaling pathway