lncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in TNBC cells via the miR-224-5p/HOXA9 axis

Abstract

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study investigated the molecular mechanism and influences of MIR503HG, miR-224-5p, and homeobox A9 (HOXA9) on TNBC cell growth and migration. Dual-luciferase reporter gene and RNA immunoprecipitation were performed to examine the regulation of MIR503HG, miR-224-5p, and HOXA9. Cell proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays. Finally, nude mice were employed to investigate the influence of MIR503HG on TNBC tumor growth. HOXA9 protein levels were detected by immunohistochemical staining. MIR503HG and HOXA9 expression were reduced in TNBC, while miR-224-5p was increased. Overexpression of MIR503HG or HOXA9 reduced the cell migration ability and proliferation and promoted apoptosis, and knockdown of MIR503HG or overexpression of miR-224-5p exhibited the opposite effects. Furthermore, MIR503HG promoted HOXA9 expression by inhibiting miR-224-5p. Overexpression of miR-224-5p reversed the effects of MIR503HG overexpression on TNBC cells, while overexpression of HOXA9 reversed the effect of MIR503HG knockdown. Additionally, an in vivo study proved that MIR503HG inhibited TNBC tumor growth via the miR-224-5p/HOXA9 axis. MIR503HG inhibited cell proliferation and promoted the apoptosis of TNBC cells via the miR-224-5p/HOXA9 axis, which may function as a novel target for the treatment of TNBC.

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

“…Low MIR503HG expression was detected in TNBC tissues, and in MDA-MB-231 and TB549 TNBC tissues, in which MIR503HG serves as a tumor suppressor [ 222 , 223 ]. Low MIR503HG expression was associated with a worse prognosis and was correlated with clinical stage, LN metastasis, and distant metastasis in TNBC patients.…”

“…In vitro upregulation of MIR503HG inhibited MDA-MB-231 and MDA-MB-453 TNBC cell migration and invasion. Two pathways—the miR-103/ OLFM4 axis and the miR-224-5p/HOXA9 axis [ 222 ]—have been implicated in mediating the functions of MIR503HG [ 223 ]. Network analysis showed ERRα to regulate MIR503HG ( Figure 9 ).…”

Circular RNA circFGFR1 Functions as an Oncogene in Glioblastoma Cells through Sponging to hsa-miR-224-5p

“…At the same time, it also has proved to promote tumor progression in papillary thyroid carcinoma [37] and cystadenocarcinoma [38] or to promote cell survival in breast cancer [39]. Furthermore, hsa-miR-224-5p could be sponged by lncRNA and circRNAs in difference cancers, for instance, by lncNEAT1 in melanoma to promote tumor development [40] or by lncRNA MIR503HG in triple-negative breast cancer to prevent tumor progression [41] or by hsa_circ_ 0017639 in gastric cancer as a promotor [42] or circ-ITCH in hepatocellular carcinoma as a suppressor [43]. Notably, The RNA enrichment of circFGFR1, hsa-miR-224-5p, and CXCR4 in SNB19 cells after immunoprecipitated with anti-AGO2 antibody using RIP assay.…”

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

“… 65 , 66 , 67 , 68 lncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in triple-negative breast cancer (TNBC) cells via the miR-224-5p/HOXA9 axis. 69 lncITPF (long non-coding idiopathic pulmonary fibrosis) promotes pulmonary fibrosis by targeting hnRNP-L depending on its host gene ITGBL1. 70 lncRNA LINC00858 functions through the miR-153-3p/Rabl3 axis, which promotes cell proliferation and infiltration in HCC.…”