LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification

Abstract

BackgroundLong noncoding RNAs (lncRNAs) can affect the progression of various tumors, including nasopharyngeal carcinoma (NPC). Here, lncRNA FOXD3-AS1 is highly expressed in NPC tissues through bioinformatics analysis and related to the malignant progression of NPC.MethodsBioinformatics analysis and real-time reverse transcription quantitative PCR(RT-qPCR) assay were applied to identify the expression of FOXD3-AS1 in NPC tissues and cells. Specific short hairpin RNAs (shRNAs) or overexpression plasmids were used to knockdown or upregulate FOXD3-AS1 in NPC cells. The effect of FOXD3-AS1 on proliferation and metastasis of NPC was confirmed by CCK8, colony formation, transwell assays in vitro and mouse tumor growth and metastasis models in vivo, of which the mechanism was explored by RNA pull down, mass spectrometry (MS), RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and luciferase assays.ResultsFOXD3-AS1 was highly expressed in NPC tissues and cells. Knockdown of FOXD3-AS1 significantly inhibited proliferation, migration, and invasion of NPC cells in vitro and vivo. FOXD3-AS1 could specifically bind to YBX1 and have a positive effect on the expression of YBX1. Bioinformatics analysis showed that the promoter of YBX1 had a high enrichment of H3K27ac, which promote mRNA transcription and protein translation of YBX1. Moreover, overexpression of YBX1 could reverse the proliferation, migration and invasion arrest caused by FOXD3-AS1 knockdown.ConclusionLncRNA FOXD3-AS1 is highly expressed and promotes malignant phenotype in NPC, which may provide a new molecular mechanism for NPC.

Evaluation of lncRNA FOXD3-AS1 as a Biomarker for Early-Stage Lung Cancer Diagnosis and Subtype Identification

“…FOXD3-AS1 has been shown to have predictive value and functional roles in various diseases, including breast cancer, cervical cancer, nasopharyngeal carcinoma, cerebral ischemia/reperfusion injury, cardiomyocyte injury, allergic rhinitis, and so on [ 15 – 17 , 27 , 28 ]. Furthermore, FOXD3-AS1 has been found in nuclear or cytoplasm fractions, and its molecular mechanisms include acting as competing endogenous RNA [ 15 , 29 ], acting as mediators for gene promotor loci and histone modification factor interaction [ 19 ], stimulating proteins expression [ 20 ], interacting and sequestering proteins, and so on [ 14 , 18 ]. In this study, we found that FOXD3-AS1 was upregulated in all primary subtypes of LC at an early stage and increased as the disease progressed.…”

“…[15-17, 27, 28]. Furthermore, FOXD3-AS1 has been found in nuclear or cytoplasm fractions, and its molecular mechanisms include acting as competing endogenous RNA [15,29], acting as mediators for gene promotor loci and histone modification factor interaction [19], stimulating proteins expression [20], interacting and sequestering proteins, and so on [14,18]. In this study, we found that FOXD3-AS1 was upregulated in all primary subtypes of LC at an early stage and increased as the disease progressed.…”

“…FOXD3-AS1 binds to poly (ADP-ribose) polymerase 1 in neuroblastoma, preventing the CCCTC-binding factor from being PARylated and thus derepressing the production of downstream tumor-suppressive genes [ 18 ]. According to Yang's research, FOXD3-AS1 binds to Y-box binding protein 1 to mediate the H3K27ac enrichment in the promoter region in nasopharyngeal carcinoma [ 19 ]. Through the PI3K/Akt pathway, FOXD3-AS1 interacts with and activates RNA-binding protein ELAV-like RNA-binding protein 1, causing LC cell proliferation, invasion, and 5-fluorouracil resistance [ 20 ].…”

Multiwalled Carbon Nanotubes-Reprogrammed Macrophages Facilitate Breast Cancer Metastasis via NBR2/TBX1 Axis

“…Furthermore, we identified that TBX1 was regulated by NBR2 through H3K27 acetylation (H3K27ac). As one of the most typical histone modifications, H3K27ac was an important epigenetic mechanism involved in the action mode of long noncoding RNA to regulate gene expression. − As reported formerly, H3K27ac mediated the regulation of ITGB8 by LINC00472 in renal clear cell carcinoma; DACT1 was regulated by LncRNA CRNDE through H3K27ac in osteoarthritis; FOXD3-AS1 increased the expression of YBX1 by enriching H3K27ac in nasopharyngeal carcinoma . We herein examined whether H3K27ac also mediated the regulation of TBX1 by NBR2 in MWCNTs-stimulated macrophages.…”

Y‐box binding protein 1 influences zygotic genome activation by regulating N6‐methyladenosine in porcine embryos

“…YBX1 is associated with histone modification. H3K27ac is highly enriched in the YBX1 promoter and promotes YBX1 mRNA transcription and protein translation (Yang et al, 2021). YBX1 can also activate p300 and alter histone acetylation landscape to promote chromatin relaxation (Davies et al, 2014).…”