PHD Finger Protein 19 Enhances the Resistance of Ovarian Cancer Cells to Compound Fuling Granule by Protecting Cell Growth, Invasion, Migration, and Stemness

Ruan, Shanming; Zhang, Haizhong; Tian, Xinxin; Zhang, Zhiqian; Huang, Hong; Shi, Chao; Liu, Wenhong; Jiang, Xin; Huang, Dawei; Tao, Fangfang

doi:10.3389/fphar.2020.00150

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…PHD finger protein 19 (PHF19), namely PCL3, is an critical component of PRC2 that acts as a transcriptional repressor of several developmentally regulated genes and functions as a pivotal regulator of various biological processes ( 14 ). PHF19 protein contains a single Tudor domain followed by two plant homeodomain (PHD) fingers and an extended homologous (EH) domain, and binds trimethylated histone H3 Lys36 (H3K36me3) through its Tudor domain ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

et al. 2022

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BackgroundAs a crucial constituent part of Polycomb repressive complex 2, PHD finger protein 19 (PHF19) plays a pivotal role in epigenetic regulation, and acts as a critical regulator of multiple pathophysiological processes. However, the exact roles of PHF19 in cancers remain enigmatic. The present research was primarily designed to provide the prognostic landscape visualizations of PHF19 in cancers, and study the correlations between PHF19 expression and immune infiltration characteristics in tumor microenvironment.MethodsRaw data in regard to PHF19 expression were extracted from TCGA and GEO data portals. We examined the expression patterns, prognostic values, mutation landscapes, and protein-protein interaction network of PHF19 in pan-cancer utilizing multiple databases, and investigated the relationship of PHF19 expression with immune infiltrates across TCGA-sequenced cancers. The R language was used to conduct KEGG and GO enrichment analyses. Besides, we built a risk-score model of hepatocellular carcinoma (HCC) and validated its prognostic classification efficiency.ResultsOn balance, PHF19 expression was significantly higher in cancers in comparison with that in noncancerous samples. Increased expression of PHF19 was detrimental to the clinical prognoses of cancer patients, especially HCC. There were significant correlations between PHF19 expression and TMB or MSI in several cancers. High PHF19 levels were critically associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that PHF19 participated in regulating carcinogenic processes including cell cycle and DNA replication, and was correlated with the progression of HCC. Intriguingly, GSEA suggested that PHF19 was correlated with the cellular components including immunoglobulin complex and T cell receptor complex in HCC. Based on PHF19-associated functional gene sets, an eleven-gene prognostic signature was constructed to predict HCC prognosis. Finally, we validated pan-cancer PHF19 expression, and its impacts on immune infiltrates in HCC.ConclusionThe epigenetic related regulator PHF19 participates in the carcinogenic progression of multiple cancers, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that PHF19 can serve as a carcinogenic indicator related to prognosis in pan-cancer, especially HCC, and shed new light on therapeutics of cancers for clinicians.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

et al. 2022

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“…PHF19 is a member of polycomb repressive complex 2 Complex, which mediates transcriptional repression of developmental regulatory genes and modulates embryonic stem cell differentiation. A recent report suggests that MIR211 can target PHF19 and thereby inhibit cell proliferation, migration and apoptosis in ovarian cancer ( 89 ). At the same time, MALAT1, a long non-coding RNA antagonizes the effect of MIR211 in ovarian cancer cells ( 46 ).…”

Section: Broadly Pleiotropic Tumor Suppressor and Oncogenic Behavior mentioning

confidence: 99%

The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers

2021

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Cancer initiation, progression, and metastasis leverage many regulatory agents, such as signaling molecules, transcription factors, and regulatory RNA molecules. Among these, regulatory non-coding RNAs have emerged as molecules that control multiple cancer types and their pathologic properties. The human microRNA-211 (MIR211) is one such molecule, which affects several cancer types, including melanoma, glioblastoma, lung adenocarcinomas, breast, ovarian, prostate, and colorectal carcinoma. Previous studies suggested that in certain tumors MIR211 acts as a tumor suppressor while in others it behaves as an oncogenic regulator. Here we summarize the known molecular genetic mechanisms that regulate MIR211 gene expression and molecular pathways that are in turn controlled by MIR211 itself. We discuss how cellular and epigenetic contexts modulate the biological effects of MIR211, which exhibit pleiotropic effects. For example, up-regulation of MIR211 expression down-regulates Warburg effect in melanoma tumor cells associated with an inhibition of the growth of human melanoma cells in vitro, and yet these conditions robustly increase tumor growth in xenografted mice. Signaling through the DUSP6-ERK5 pathway is modulated by MIR211 in BRAFV600E driven melanoma tumors, and this function is involved in the resistance of tumor cells to the BRAF inhibitor, Vemurafenib. We discuss several alternate but testable models, involving stochastic cell-to-cell expression heterogeneity due to multiple equilibria involving feedback circuits, intracellular communication, and genetic variation at miRNA target sties, to reconcile the paradoxical effects of MIR211 on tumorigenesis. Understanding the precise role of this miRNA is crucial to understanding the genetic basis of melanoma as well as the other cancer types where this regulatory molecule has important influences. We hope this review will inspire novel directions in this field.

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“…PHF19 is overexpressed in a number of human cancers including prostate cancer [35], glioblastoma, [36,37], hepatocellular carcinoma [30,[38][39][40], ovarian cancer [41,42], melanoma [22,43], gastric cancer [44][45][46]. EWS/ ETS-driven Ewing sarcoma [47] and colorectal cancer [48].…”

Section: Alterations Of Phf19 Expression In Cancermentioning

confidence: 99%

Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer

Ghamlouch

Boyle

Blaney

et al. 2021

J Exp Clin Cancer Res

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Despite improvements in outcome, 15-25% of newly diagnosed multiple myeloma (MM) patients have treatment resistant high-risk (HR) disease with a poor survival. The lack of a genetic basis for HR has focused attention on the role played by epigenetic changes. Aberrant expression and somatic mutations affecting genes involved in the regulation of tri-methylation of the lysine (K) 27 on histone 3 H3 (H3K27me3) are common in cancer. H3K27me3 is catalyzed by EZH2, the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). The deregulation of H3K27me3 has been shown to be involved in oncogenic transformation and tumor progression in a variety of hematological malignancies including MM. Recently we have shown that aberrant overexpression of the PRC2 subunit PHD Finger Protein 19 (PHF19) is the most significant overall contributor to HR status further focusing attention on the role played by epigenetic change in MM. By modulating both the PRC2/EZH2 catalytic activity and recruitment, PHF19 regulates the expression of key genes involved in cell growth and differentiation. Here we review the expression, regulation and function of PHF19 both in normal and the pathological contexts of solid cancers and MM. We present evidence that strongly implicates PHF19 in the regulation of genes important in cell cycle and the genetic stability of MM cells making it highly relevant to HR MM behavior. A detailed understanding of the normal and pathological functions of PHF19 will allow us to design therapeutic strategies able to target aggressive subsets of MM.

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PHD Finger Protein 19 Enhances the Resistance of Ovarian Cancer Cells to Compound Fuling Granule by Protecting Cell Growth, Invasion, Migration, and Stemness

Cited by 6 publications

References 26 publications

Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers

Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer

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