HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol

Abstract

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

Sevoflurane induces inflammation in primary hippocampal neurons by regulating Hoxa5/Gm5106/miR-27b-3p positive feedback loop

“…Both two motifs were required for Hoxa5 transcription ability. Hoxa5 usually plays tumor promotion roles in severe diseases such as breast cancer [ 25 ], acute myeloid leukemia [ 26 ] and colorectal cancer [ 27 ]. Notably, HOXA5 is also correlated to immune response involving M2 macrophage and TGF-β signaling pathways [ 28 ].…”

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma

“…The role of HOXA4 and HOXA5 in the occurrence and progression of a variety of human cancers has been scatteredly reported in previous literature studies [7,8,22,23]. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD.…”

“…These proteins regulate early embryo segmentation patterns and late developmental events [6]. There is literature evidence that the abnormal expression of HOXA family genes including HOXA4 and HOXA5 is closely related to the occurrence and development of diverse human cancers including breast cancer, colorectal cancer and ovarian cancer [7][8][9]. HOXA5 was discovered to present overexpression in breast cancer and served as a prognostic biomarker for colorectal cancer [7][8].…”

“…There is literature evidence that the abnormal expression of HOXA family genes including HOXA4 and HOXA5 is closely related to the occurrence and development of diverse human cancers including breast cancer, colorectal cancer and ovarian cancer [7][8][9]. HOXA5 was discovered to present overexpression in breast cancer and served as a prognostic biomarker for colorectal cancer [7][8]. The work of Klausen et al demonstrated the inhibiting effect of HOXA4 on the cell motility and spreading of ovarian cancer cells [9].…”

Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention

“…HOX proteins encoded by HOX genes are key components of substantial metabolic processes such as lipidic metabolism, and their [brain cancer mainly includes the glioma and neuroblastoma (4)(5)(6)(7)(8)(9)(10)(11), lung cancer (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), hepatocellular carcinoma (25)(26)(27)(28)(29)(30)(31), bladder cancer (32,33), cholangiocarcinoma (34), head and neck squamous cell carcinoma (35,36), breast cancer (21)(22)(23)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)…”