“…Furthermore, ZNF217 is a downstream target of miR-182-5p. 84 In keloid fibroblasts, long non-coding RNA HOXA11-AS indirectly regulates the expression of ZNF217 by competitively binding to miR-182-5p, which in turn controls the formation and development of keloids 84 (Figure 4).…”
Section: Long Non-coding Rna Regulates the Expression Of Znf217mentioning
confidence: 99%
“…Furthermore, ZNF217 is a downstream target of miR-182-5p. 84 In keloid fibroblasts, long non-coding RNA HOXA11-AS indirectly regulates the expression of ZNF217 by competitively binding to miR-182-5p, which in turn controls the formation and development of keloids 84 ( Figure 4 ). Figure 4 LncRNA inhibits the negative regulation of ZNF217 by miRNA either by acting as a miRNA sponge or directly promoting ZNF217 expression.…”
Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment.
“…Furthermore, ZNF217 is a downstream target of miR-182-5p. 84 In keloid fibroblasts, long non-coding RNA HOXA11-AS indirectly regulates the expression of ZNF217 by competitively binding to miR-182-5p, which in turn controls the formation and development of keloids 84 (Figure 4).…”
Section: Long Non-coding Rna Regulates the Expression Of Znf217mentioning
confidence: 99%
“…Furthermore, ZNF217 is a downstream target of miR-182-5p. 84 In keloid fibroblasts, long non-coding RNA HOXA11-AS indirectly regulates the expression of ZNF217 by competitively binding to miR-182-5p, which in turn controls the formation and development of keloids 84 ( Figure 4 ). Figure 4 LncRNA inhibits the negative regulation of ZNF217 by miRNA either by acting as a miRNA sponge or directly promoting ZNF217 expression.…”
Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment.
“…Keloids are considered to be benign skin tumors, with uncontrolled fibroblast proliferation and low remission rate [ 99 ]. By positively regulating ZNF217 expression after decoying miR-182-5p, the lncRNA HOXA11-AS regulates the miR-182-5p/ZNF217 axis to induce the proliferation and migration of keloid fibroblasts in vitro , while promoting keloid formation and growth in mouse [ 100 ].…”
“…Briefly, an HOXB13/HOXA11-AS axis regulates BM-related integrin and CCL2/CCR2 cytokine signaling in PCa cells, while paracrine action of exosomal HOXA11-AS secreted from PCa cells is able to modulate CCL2/CCR2 cytokine signaling in osteoblasts within the bone marrow milieu [ 136 ]. LncRNA MALAT1 and lncRNA HOXA11-AS promote the activation of the ZNF217-dependent functions after sponging miR-141-3p [ 79 ] and miR-182-5p [ 100 ], respectively. It is, thus, tempting to speculate that MALAT1/miR141-3p/ZNF217 or HOXA11-AS/miR182-5p/ZNF217 axes might exist in PCa tumors, contributing to the development of BM.…”
Section: Ncrnas Network Targeting Znf217 Are Also Involved In Program...mentioning
The oncogenic transcription factor ZNF217 orchestrates several molecular signaling networks to reprogram integrated circuits governing hallmark capabilities within cancer cells. High levels of ZNF217 expression provide advantages to a specific subset of cancer cells to reprogram tumor progression, drug resistance and cancer cell plasticity. ZNF217 expression level, thus, provides a powerful biomarker of poor prognosis and a predictive biomarker for anticancer therapies. Cancer epigenetic mechanisms are well known to support the acquisition of hallmark characteristics during oncogenesis. However, the complex interactions between ZNF217 and epigenetic processes have been poorly appreciated. Deregulated DNA methylation status at ZNF217 locus or an intricate cross-talk between ZNF217 and noncoding RNA networks could explain aberrant ZNF217 expression levels in a cancer cell context. On the other hand, the ZNF217 protein controls gene expression signatures and molecular signaling for tumor progression by tuning DNA methylation status at key promoters by interfering with noncoding RNAs or by refining the epitranscriptome. Altogether, this review focuses on the recent advances in the understanding of ZNF217 collaboration with epigenetics processes to orchestrate oncogenesis. We also discuss the exciting burgeoning translational medicine and candidate therapeutic strategies emerging from those recent findings connecting ZNF217 to epigenetic deregulation in cancer.
“…High expression of lncRNA homeobox A11 antisense (HOXA11-AS) was reported to be associated with poor prognosis in ESCC [29]. Notably, HOXA11-AS regulated target gene expressions in tumorigenesis through interacting with the transcription factor FOXP2, histone methyltransferase EZH2, histone demethylase LSD1 or DNMT1 [30,31].Whereas, events in which lncRNAs are regulated as targets of AS have rarely been revealed. Aerobic glycolysis, also called the Warburg effect, has always been considered a hallmark and driving force for tumors [32][33][34].Abnormally expressed glycolytic enzymes and glucose transporters are wellknown for triggering the glycolysis phenotype, and the suppression of these factors restrains tumorigenesis and reverses chemoresistance [35][36][37].…”
Background
Dysregulated splicing factors (SFs) and aberrant alternative splicing (AS) events are involved in tumor progression. However, the AS landscape underlying SFs dysregulation and the further signal transduction network were unraveled in esophageal squamous cell carcinoma (ESCC). This study revealed the biological function of splicing factor 3b subunit 4 (SF3B4) in non-coding RNA AS and glycolytic reprogramming, and proposed a novel diagnostic pannel and therapeutic targets for ESCC.
Methords
The expression, diagnostic efficiency and prognostic value of SF3B4 were investigated by bioinformatics, real-time fluorescent quantitative PCR and immunohistochemistry assays. The biological functions of SF3B4 in ESCC were analyzed in vivo and in vitro by loss-of-function studies. RNA sequencing, minigene reporter, RNA immunoprecipitation and correlation analysis were performed to elucidate SF3B4-regulated AS isoforms and SF3B4-interaction motif. Seahorse metabolism assays and high performance liquid chromatography-mass spectrometry analysis were conducted to explore the potential molecular mechanism of SF3B4 and downstream AS isoforms in driving ESCC development.
Results
SF3B4 was significantly up-regulated in ESCC and facilitated cell proliferation, survival, cycle progression and cisplatin resistance. Mechanically, SF3B4 increased proportion of the tumorigenic splicing isoform (HOX-L) of long noncoding RNA homeobox A11 antisense (HOXA11-AS), which resulted in enhanced glycolysis and elevated transcription of glycolytic enzyme PKM2, ENO1, HK2, GLUT1, LDHA and PGK1, through promoting phosphorylation of β-catenin at serine 675 and activation of Wnt pathway. Remarkably, inhibition of glycolysis reversed the malignant phenotype induced by the SF3B4-HOX-L axis. Moreover, the RNA levels of SF3B4 and HOX-L were positively correlated with ESCC tumor volume, and high SF3B4 expression demonstrated significant poor survival for ESCC patients. Additionally, the combination of SF3B4 and HOXA11-AS expression also showed good diagnostic performance.
Conclusions
These findings highlighted the oncogenic role of the SF3B4-HOX-L- Wnt-β-catenin-glycolytic enzyme axis in ESCC development, and proposed SF3B4 and HOX-L splicing isoform as novel therapeutic targets and diagnostic biomarkers for ESCC.
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