Multi-omics analysis reveals CMTR1 upregulation in cancer and roles in ribosomal protein gene expression and tumor growth.

The mRNA cap methyltransferase CMTR1 plays a crucial role in RNA metabolism and gene expression regulation, yet its significance in cancer remains largely unexplored. Here, we present a comprehensive multi-omics analysis of CMTR1 across various human cancers, revealing its widespread upregulation and potential as a therapeutic target. Integrating transcriptomic and proteomic data from a large set of cancer samples, we demonstrate that CMTR1 is upregulated at the mRNA, protein, and phosphoprotein levels across multiple cancer types.

KDM4 Demethylases: Structure, Function, and Inhibitors.

KDM4 histone demethylases mainly catalyze the removal of methyl marks from H3K9 and H3K36 to epigenetically regulate chromatin structure and gene expression. KDM4 expression is strictly regulated to ensure proper function in a myriad of biological processes, including transcription, cellular proliferation and differentiation, DNA damage repair, immune response, and stem cell self-renewal. Aberrant expression of KDM4 demethylase has been documented in many types of blood and solid tumors, and thus, KDM4s represent promising therapeutic targets.

Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer.

Human methyltransferase-like (METTL) proteins transfer methyl groups to nucleic acids, proteins, lipids, and other small molecules, subsequently playing important roles in various cellular processes. In this study, we performed integrated genomic, transcriptomic, proteomic, and clinicopathological analyses of 34 METTLs in a large cohort of primary tumor and cell line data. We identified a subset of METTL genes, notably METTL1, METTL7B, and NTMT1, with high frequencies of genomic amplification and/or up-regulation at both the mRNA and protein levels in a spectrum of human cancers.

Structural analysis, virtual screening and molecular simulation to identify potential inhibitors targeting 2'-O-ribose methyltransferase of SARS-CoV-2 coronavirus.

SARS-CoV-2, an emerging coronavirus, has spread rapidly around the world, resulting in over ten million cases and more than half a million deaths as of July 1, 2020. Effective treatments and vaccines for SARS-CoV-2 infection do not currently exist. Previous studies demonstrated that nonstructural protein 16 (nsp16) of coronavirus is an S-adenosyl methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that has an important role in viral replication and prevents recognition by the host innate immune system.

Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features.

Lysine acetyltransferases (KATs) are a highly diverse group of epigenetic enzymes that play important roles in various cellular processes including transcription, signal transduction, and cellular metabolism. However, our knowledge of the genomic and transcriptomic alterations of KAT genes and their clinical significance in human cancer remains incomplete. We undertook a metagenomic analysis of 37 KATs in more than 10 000 cancer samples across 33 tumor types, focusing on breast cancer.

Pan-cancer analysis of RNA methyltransferases identifies FTSJ3 as a potential regulator of breast cancer progression.

RNA methylation, catalysed by a set of RNA methyltransferases (RNMTs), modulates RNA structures, properties, and biological functions. RNMTs are increasingly documented to be dysregulated in various human diseases, particularly developmental disorders and cancer. However, the genomic and transcriptomic alterations of RNMTs, as well as their functional roles in human cancer, are limited.

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.

Background: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.

Methods: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis.

Loss of mdig expression enhances DNA and histone methylation and metastasis of aggressive breast cancer.

We previously reported that expression of an environmentally induced gene, mineral dust-induced gene (), predicts overall survival in breast cancer patients. In the present report, we further demonstrate the differential roles of mdig between earlier- and later-stage breast cancers. In noncancerous breast, mdig is a proliferation factor for cell growth and cell motility.

Impaired epidermal Langerhans cell maturation in TGFβ-inducible early gene 1 (TIEG1) knockout mice.

TGF-β-inducible early gene 1 (TIEG1), also known as Krüppel-like factor 10 (Klf10), represents a major downstream transcription factor of transforming growth factor-β1 (TGF-β1) signaling. Epidermal Langerhans cells (LCs), a unique subpopulation of dendritic cells (DC), essentially mediates immune surveillance and tolerance. TGF-β1 plays a pivotal role in LC maintenance and function after birth, although the underpinning mechanisms remain elusive.

Genotranscriptomic meta-analysis of the CHD family chromatin remodelers in human cancers - initial evidence of an oncogenic role for CHD7.

Chromodomain helicase DNA binding proteins (CHDs) are characterized by N-terminal tandem chromodomains and a central adenosine triphosphate-dependent helicase domain. CHDs govern the cellular machinery's access to DNA, thereby playing critical roles in various cellular processes including transcription, proliferation, and DNA damage repair. Accumulating evidence demonstrates that mutation and dysregulation of CHDs are implicated in the pathogenesis of developmental disorders and cancer.

Integrative genomic and transcriptomic analysis for pinpointing recurrent alterations of plant homeodomain genes and their clinical significance in breast cancer.

A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer.

Inositol-Requiring Enzyme 1 Facilitates Diabetic Wound Healing Through Modulating MicroRNAs.

Diabetic skin ulcers represent a challenging clinical problem with mechanisms not fully understood. In this study, we investigated the role and mechanism for the primary unfolded protein response (UPR) transducer inositol-requiring enzyme 1 (IRE1α) in diabetic wound healing. Bone marrow-derived progenitor cells (BMPCs) were isolated from adult male type 2 diabetic and their littermate control mice.

COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells.

Post-Transcriptional Regulation of the GASC1 Oncogene with Active Tumor-Targeted siRNA-Nanoparticles.

Basal-like breast cancer (BLBC) accounts for the most aggressive types of breast cancer, marked by high rates of relapse and poor prognoses and with no effective clinical therapy yet. Therefore, investigation of new targets and treatment strategies is more than necessary. Here, we identified a receptor that can be targeted in BLBC for efficient and specific siRNA mediated gene knockdown of therapeutically relevant genes such as the histone demethylase GASC1, which is involved in multiple signaling pathways leading to tumorigenesis.

An integrated genomic analysis of Tudor domain-containing proteins identifies PHD finger protein 20-like 1 (PHF20L1) as a candidate oncogene in breast cancer.

Tudor domain-containing proteins (TDRDs), which recognize and bind to methyl-lysine/arginine residues on histones and non-histone proteins, play critical roles in regulating chromatin architecture, transcription, genomic stability, and RNA metabolism. Dysregulation of several TDRDs have been observed in various types of cancer. However, neither the genomic landscape nor clinical significance of TDRDs in breast cancer has been explored comprehensively.

Histone lysine demethylases in Drosophila melanogaster.

Epigenetic regulation of chromatin structure is a fundamental process for eukaryotes. Regulators include DNA methylation, microRNAs and chromatin modifications. Within the chromatin modifiers, one class of enzymes that can functionally bind and modify chromatin, through the removal of methyl marks, is the histone lysine demethylases.

Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer.

Histone lysine demethylases (KDMs) comprise a large class of enzymes that catalyze site-specific demethylation of lysine residues on histones and other proteins. They play critical roles in controlling transcription, chromatin architecture, and cellular differentiation. However, the genomic landscape and clinical significance of KDMs in breast cancer remain poorly characterized.

Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer.

The histone lysine demethylase KDM4 subfamily, comprised of four members (A, B, C, and D), play critical roles in controlling transcription, chromatin architecture and cellular differentiation. We previously demonstrated that KDM4C is significantly amplified and overexpressed in aggressive basal-like breast cancers and functions as a transforming oncogene. However, information regarding the genomic and transcriptomic alterations of the KDM4 subfamily in different subtypes of breast cancer remains largely incomplete.

A novel ER-microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression.

The gene encoding endoplasmic reticulum (ER) lipid raft-associated protein 2 (ERLIN2) is amplified in human breast cancers. ERLIN2 gene mutations were also found to be associated with human childhood progressive motor neuron diseases. Yet, an understanding of the physiological function and mechanism for ERLIN2 remains elusive.

Genetic alterations of histone lysine methyltransferases and their significance in breast cancer.

Histone lysine methyltransferases (HMTs), a large class of enzymes that catalyze site-specific methylation of lysine residues on histones and other proteins, play critical roles in controlling transcription, chromatin architecture, and cellular differentiation. However, the genomic landscape and clinical significance of HMTs in breast cancer remain poorly characterized. Here, we conducted a meta-analysis of approximately 50 HMTs in breast cancer and identified associations among recurrent copy number alterations, mutations, gene expression, and clinical outcome.

Histone lysine demethylase (KDM) subfamily 4: structures, functions and therapeutic potential.

KDM4 histone demethylases catalyze the removal of methyl marks from histone lysine residues to epigenetically regulate chromatin structure and gene expression. KDM4 expression is tightly regulated to insure proper function in diverse biological processes, such as cellular differentiation. Mounting evidence has shown that disrupting KDM4 expression is implicated in the establishment and progression of multiple diseases including cancer.

Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma.

Gene amplified in squamous cell carcinoma 1 (GASC1) is a member of Jumonji C-domain containing histone demethylases that play an essential role in affecting chromatin architecture and gene expression. The purpose of this study was to determine the expression features and the clinical significance of GASC1 in esophageal squamous cell carcinoma (ESCC). GASC1 expression was detected on tissue microarrays of ESCC samples in 185 cases using immunohistochemical staining.

Genomic amplification and a role in drug-resistance for the KDM5A histone demethylase in breast cancer.

Lysine-specific demethylase 5A (KDM5A), an enzyme that removes activating H3K4 di- and trimethylation marks, plays critical roles in controlling transcription and chromatin architecture, yet its biological functions largely remain uncharacterized, particularly in the context of human cancer. In the present study, we found that the KDM5A gene was significantly amplified and over-expressed in various human tumors, including breast cancer. Reducing the expression of KDM5A by shRNA knockdown inhibited proliferation of KDM5A-amplified breast cancer cells.

Endoplasmic reticulum factor ERLIN2 regulates cytosolic lipid content in cancer cells.

Increased de novo lipogenesis is a hallmark of aggressive cancers. Lipid droplets, the major form of cytosolic lipid storage, have been implicated in cancer cell proliferation and tumorigenesis. Recently, we identified the ERLIN2 [ER (endoplasmic reticulum) lipid raft-associated 2) gene that is amplified and overexpressed in aggressive human breast cancer.