The Role of Histone Methyltransferases and Long Non-coding RNAs in the Regulation of T Cell Fate Decisions

Gaballa, Joseph M.; Neto, Manuel Bonfim Braga; Ramos, Guilherme Piovezani; Bamidele, Adebowale O.; Gonzalez, Michelle; Sagstetter, Mary R.; Sarmento, Olga F.; Faubion, William A.

doi:10.3389/fimmu.2018.02955

Cited by 15 publications

(12 citation statements)

References 108 publications

(119 reference statements)

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“…The two primary PRCs noted in mammals are PRC1, formed by several distinct proteins but most notably RING1A/B and BMI1, and PRC2. The core subunits of PRC2 are enhancer of zeste homolog 1/2 (EZH1/EZH2), embryonic ectoderm development (EED), and suppressor of zeste 12 (SUZ12) ( 1 ). Within the PRC2 complex, EZH2 (and to a lesser extent, EZH1) is the catalytic subunit responsible for methyltransferase activity.…”

Section: Introductionmentioning

confidence: 99%

EZH2 as a Regulator of CD8+ T Cell Fate and Function

2020

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Enhancer of zeste 2 (EZH2) is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) that mediates di-and trimethylation of histone 3 lysine 27 effectively precluding successful gene transcription at these loci. This class of epigenetic modifications facilitates the maintenance of tissue-specific cellular transcriptional programs as cells undergoing successive rounds of proliferation. CD8+ T cells are effective mediators of adaptive immunity and function to eliminate virus-and bacteria-infected cells as well as tumor cells. Upon recognition of cognate antigen, T cells undergo activation/proliferation to clear the target cells. The heterogeneous population of responding T cells formed during these proliferative events thus rely on epigenetic modifications to ensure identity and confer functional capabilities. In this review, we will focus on the role of the dynamic expression EZH2 in shaping the epigenetic landscape of CD8+ T cell fate and function, with a particular emphasis on infection and cancer. We also explore competing hypotheses pertaining to EZH2 function and the prospects of clinical EZH2 inhibitors in fine-tuning T cell responses.

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Section: Introductionmentioning

confidence: 99%

EZH2 as a Regulator of CD8+ T Cell Fate and Function

2020

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“…In mammals, there are two primary PRCs including PRC1 and PRC2. EZH2 is a member of PRCs that exerts functional roles in cells [ 23 ]. In PCR2 complex, EZH2 is considered as a catalytic subunit and is responsible for methyltransferase activity.…”

Section: Ezh2 Signaling In Cancermentioning

confidence: 99%

The long and short non-coding RNAs modulating EZH2 signaling in cancer

et al. 2022

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Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.

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“…Despite the optimization of current treatments, the clinical outcome of patients remains poor (4). Previous studies demonstrated that aberrantly expressed molecules in tumors play an important role in tumorigenesis and predict patient survival outcomes (11)(12)(13)(14). Cancer-specific lncRNAs have been reported to contribute to tumor progression in various types of cancer, including oesophageal cancer, pancreatic cancer, nasopharyngeal carcinoma, hepatocellular carcinoma, cervical cancer, colorectal cancer and gastric cancer (31).…”

Section: Discussionmentioning

confidence: 99%

“…lncRNAs regulate the expression level of genes on epigenetic, transcriptional and post-transcriptional levels ( 12 , 13 ). The modes of regulation by lncRNAs include chromosome modification and transcriptional activation or interference ( 14 ). Previously, these long non-coding transcripts were regarded as transcriptional ‘noise’ or cloning artifacts ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

lncRNA KTN1‑AS1 promotes glioma cell proliferation and invasion by negatively regulating miR‑505‑3p

Tang

Feng

et al. 2020

Oncol Rep

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Glioblastoma (GBM) is one of the most prevalent and aggressive central nervous tumors with high mobility and mortality. The prognosis of patients with GBM is poor. It is therefore essential to explore the therapeutic strategies for the treatment of GBM. Previous studies have demonstrated that the long non-coding RNA (lncRNA) Kinectin 1-Antisense RNA 1 (KTN1-AS1) can participate in the development of several types of cancer. However, the underlying mechanism of KTN1-AS1 in GBM remains unknown. The present study aimed to determine the potential role of KTN1-AS1 in GBM. In this study, reverse transcription quantitative PCR analysis was conducted and the results demonstrated that KTN1-AS1 was upregulated in GBM tissues and cell lines compared with normal tissues and astrocytes (NHA). Furthermore, KTN1-AS1 knockdown decreased the viability and invasive ability of glioma cells in vitro and in vivo . In addition, high level of KTN1-AS1 was correlated with poor prognosis in TCGA GBM database. Furthermore, microRNA-505-3p (miR-505-3p) was a promising target of KTN1-AS1, and the suppressing effects of miR-505-3p on cell proliferation and invasive ability was reversed by downregulating KTN1-AS1. Taken together, the results from the present provided novel insights into the roles of KTN1-AS1 in GBM, and suggested that the KTN1-AS1/miR-505-3p axis may be considered as a novel therapeutic target for the treatment of patients with GBM.

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The Role of Histone Methyltransferases and Long Non-coding RNAs in the Regulation of T Cell Fate Decisions

Cited by 15 publications

References 108 publications

EZH2 as a Regulator of CD8+ T Cell Fate and Function

EZH2 as a Regulator of CD8+ T Cell Fate and Function

The long and short non-coding RNAs modulating EZH2 signaling in cancer

lncRNA KTN1‑AS1 promotes glioma cell proliferation and invasion by negatively regulating miR‑505‑3p

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