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

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 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.

Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR‐mediated epigenetic suppression on VGLL4 by DNMT1

“…As proof, lncRNA DILA1 downregulation promoted TAM sensitivity in BC 33 . LncRNA HAGLR was previously confirmed as an oncogene in several human malignancies, including BC 13,16 . However, little is known about the role of HAGLR involved in TAM resistance in BC.…”

“…A previous study has been demonstrated that HAGLR takes an essential role to be involved in BC progression 16 . Hence, we firstly examined the expression patterns of HAGLR in the cellular level.…”

“…A previous study has been demonstrated that HAGLR takes an essential role to be involved in BC progression. 16 Hence, we firstly 2B). In order to examine whether HAGLR would be a downstream effector of lycoinemediated TAM resistance of BC, firstly, loss-of-function assay referring to HAGLR was employed for evaluating its functional role.…”

“…HOXD antisense growth‐associated lncRNA (HAGLR) is identified as an oncogene in various human malignancies, including BC 13–15 . It was previously reported that HAGLR expression was markedly increased in BC tissues and cells, and its knockdown remarkably inhibited BC cell malignant behaviors 13,16 . It is suggested that HAGLR is a risking factor affecting BC progression, however, the role of HAGLR in regulating TAM resistance in BC remains largely unknown.…”

Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway

“…It induces a cancer cell cycle, proliferation, apoptosis, tumorigenic angiogenesis, and metastasis ( Sokół et al, 2017 ). Upregulation of SRSF1 activates the Wnt pathway, promoting tumor growth ( Malakar et al, 2017 ; Zhang et al, 2021 ), which may be related to the accumulation of β-catenin proteins ( Fu et al, 2013 ). Glycogen synthase kinase-3β is a serine/threonine kinase that participates in various signaling pathways including Wnt/β-catenin.…”