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Aging Epigenetics
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Vasily V. Ashapkin, Lyudmila I. Kutueva, Boris F. Vanyushin
An analysis of miRNA expression profiles between old and young murine liver specimens revealed four miRNAs upregulated with aging, miR-669c (9.9-fold upregulation in 33-month-old mice compared with 4-month-old ones), miR-709 (7.6-fold), miR-214 (3.4-fold), and miR-93 (4.3-fold) [84]. Only miR-669c and miR-709 showed a gradual increase with age, whereas miR-93 and miR-214 showed biphasic expression at 10- and 18–33-month ages. Several miRNAs were found to decrease at 33 months compared with 10 months (miR-375, let-7i and let-7g). At least 24% of proteins significantly downregulated at 33 months appeared to be targets of the four upregulated miRNAs. Importantly, several of these proteins (Acsl1, Gstz1, Uqcrc1, and Mgst1) are linked with mitochondria. Several downregulated glutathione S-transferases are also among the predicted targets. Obviously, these miRNAs may be implicated in an aging mechanism related to oxidative stress. Specifically, a decline in oxidative protection is correlated with miR-93 targeted Mgst1, and the failure of the mitochondrial respiratory chain is correlated with miR-709 targeted Uqcrc1. Insulin-like growth factor 1 (Igf1) is among the predicted targets of miR-93; it may have a role in the IIS pathway similar to lin-4 in C. elegans. Decreased IIS pathway activity is intrinsically related to conditions of CR and may influence longevity. The gene for miR-669c is located in an intron of the gene encoding Sfmbt2, a Polycomb group (PcG) protein, known to functionally interact with TF Yinyang1 (YY1), possibly forming a PcG silencing complex [85]. The gene for miR-709 is found in an intron of the gene encoding TF Rfx1, a known activator of the virus gene expression and suppressor of cellular genes, such as c-myc and PCNA. One of the miR-709 targets is Brother of the Regulator of Imprinted Sites (BORIS), known to play an important role in epigenetic reprogramming during the male germ cell differentiation [86]. Its downregulation by miR-709 may be the cause of age-dependent decline in spermatogenesis.
Recent advances in molecular biomarkers for patients with hepatocellular carcinoma
Published in Expert Review of Molecular Diagnostics, 2019
Shinichi Umeda, Mitsuro Kanda, Yasuhiro Kodera
Regulatory factor X1 (RFX1) is characterized by a highly conserved DNA-binding domain [56] that binds the X-box consensus sequence in promoter regions to regulate gene expression [57]. Liu et al. revealed that RFX1 levels were downregulated in HCC tissues and that low RFX1 levels correlated with vascular invasion and tumor size [41]. Moreover, they found that RFX1 levels in HCC tissues were negatively correlated with poor prognosis of HCC patients, especially for patients with small HCC. siRNA-mediated knockdown of RFX1 decreased E-cadherin and increased vimentin expression, while lentivirus vector-mediated RFX1 knockin produced the opposite result, indicating the involvement of RFX1 in EMT [41]. They concluded that RFX1 is a novel biomarker for prognosis and recurrence risk for patients with small HCC.
DNA methylation changes on immune cells in Systemic Lupus Erythematosus
Published in Autoimmunity, 2020
Carolina Hurtado, Liliana Yazmín Acevedo Sáenz, Elsa María Vásquez Trespalacios, Rodrigo Urrego, Scott Jenks, Iñaki Sanz, Gloria Vásquez
RFX1 is a transcription factor believed to be able to bind to DNMT1 and recruit it to the promoter region of both CD11a and CD70. RFX1 was found to be downregulated in CD4+ T cells of patients with lupus, and this was associated with an increase in CD11a and CD70, as well as B cell activation and IgG production [32]. Also, RFX1 is regulated by STAT3 pathway and has a direct effect on IL-17A production. Specifically, RFX1 has an inhibitory effect on IL-17A, through epigenetic mechanisms. Then, the down-regulation of RFX1 could lead to a lupus flare due to the increased IL-17A [33], because IL-17 has a proinflammatory effect, inducing the production pro-inflammatory cytokines and chemotaxis [34].