Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis.

Published on Aug 28, 2017in Oncogene9.867
· DOI :10.1038/ONC.2017.285
S. K. Hong7
Estimated H-index: 7
Sources
Abstract
RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.
Figures & Tables
Download
📖 Papers frequently viewed together
20140.35Oncotarget
16 Authors (Kwang Soo Lee, ..., Yong Sun Lee)
201813.50bioRxiv
References60
Newest
#1Jong Lyul Park (Korea Research Institute of Bioscience and Biotechnology)H-Index: 11
#2Young-Jong LeeH-Index: 1
Last. Yong Sun LeeH-Index: 17
view all 5 authors...
RNA polymerase III (Pol III) synthesizes a range of medium-sized noncoding RNAs (collectively ‘Pol III genes’) whose early established biological roles were so essential that they were considered ‘housekeeping genes’. Besides these fundamental functions, diverse unconventional roles of mammalian Pol III genes have recently been recognized and their expression must be exquisitely controlled. In this review, we summarize the epigenetic regulation of Pol III genes by chromatin structure, histone mo...
Source
// Eun Kyung Lee 1, * , Seung-Hyun Hong 2, * , Sooyong Shin 3, 4, * , Hyun-Sung Lee 5 , Ju-Seog Lee 6 , Eun Jung Park 7, 8 , Sun Shim Choi 9 , Jae Woong Min 9 , Daeyoon Park 1 , Jung-Ah Hwang 2 , Betty H. Johnson 3 , Sung Ho Jeon 4 , In-Hoo Kim 8 , Yeon-Su Lee 2 , Yong Sun Lee 3, 8 1 Center for Thyroid Cancer, National Cancer Center, Goyang, 410-769, Korea 2 Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, 410-769, Korea 3 Department of Biochemistry and Molecular Biolo...
Source
#1William C. Hines (LBNL: Lawrence Berkeley National Laboratory)H-Index: 15
#2Irene Kuhn (LBNL: Lawrence Berkeley National Laboratory)H-Index: 6
Last. Mina J. Bissell (LBNL: Lawrence Berkeley National Laboratory)H-Index: 138
view all 10 authors...
Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER+) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xe...
Source
#1Yu Fu (UTMB: University of Texas Medical Branch)H-Index: 2
#2Inhan LeeH-Index: 2
Last. Xiaoyong BaoH-Index: 23
view all 4 authors...
tRNA-derived RNA fragments (tRFs) are an emerging class of non-coding RNAs (ncRNAs). A growing number of reports have shown that tRFs are not random degradation products but are functional ncRNAs made of specific tRNA cleavage. They play regulatory roles in several biological contexts such as cancer, innate immunity, stress responses, and neurological disorders. In this review, we summarize the biogenesis and functions of tRFs.
Source
#1Matt J. Silver (Lond: University of London)H-Index: 18
#2Noah J. Kessler (BCM: Baylor College of Medicine)H-Index: 8
Last. Robert A. Waterland (BCM: Baylor College of Medicine)H-Index: 44
view all 18 authors...
Background: Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants. Results: First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a g...
Source
#1Dhaval Varshney (Glas.: University of Glasgow)H-Index: 5
#2Jana Vavrova-Anderson (Glas.: University of Glasgow)H-Index: 3
Last. Robert J. White (Glas.: University of Glasgow)H-Index: 54
view all 6 authors...
Short interspersed nuclear elements (SINEs), such as Alu, spread by retrotransposition, which requires their transcripts to be copied into DNA and then inserted into new chromosomal sites. This can lead to genetic damage through insertional mutagenesis and chromosomal rearrangements between non-allelic SINEs at distinct loci. SINE DNA is heavily methylated and this was thought to suppress its accessibility and transcription, thereby protecting against retrotransposition. Here we provide several ...
Source
#1Jonathan K. Lee (LBNL: Lawrence Berkeley National Laboratory)H-Index: 4
#2James C. Garbe (LBNL: Lawrence Berkeley National Laboratory)H-Index: 28
Last. Mark A. LaBarge (LBNL: Lawrence Berkeley National Laboratory)H-Index: 26
view all 7 authors...
Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary...
Source
#1James C. Garbe (LBNL: Lawrence Berkeley National Laboratory)H-Index: 28
#2Lukas Vrba (UA: University of Arizona)H-Index: 20
Last. Martha R. Stampfer (LBNL: Lawrence Berkeley National Laboratory)H-Index: 68
view all 12 authors...
Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to the paucity of experimentally tractable model systems that can examine human epithelial cell immortalization as it might occur in vivo. We achieved efficient non-clonal immortalization of normal human mammary epithelial cells (HMEC) by directly targeting the 2 main senescence barriers encountered by cultured HMEC. Th...
Source
#1Kwang Soo Lee (UTMB: University of Texas Medical Branch)H-Index: 4
#2Jong Lyul Park (Korea Research Institute of Bioscience and Biotechnology)H-Index: 11
Last. Yong Sun Lee (UTMB: University of Texas Medical Branch)H-Index: 17
view all 16 authors...
// Kwang-Soo Lee 1,2,* , Jong-Lyul Park 3,4,* , Kwanbok Lee 1 , Lauren E. Richardson 1,5 , Betty H. Johnson 1 , Hyun-Sung Lee 6 , Ju-Seog Lee 6 , Sang-Bae Kim 6 , Oh-Hyung Kwon 3 , Kyu Sang Song 7 , Yong Sung Kim 3,4 , Hassan Ashktorab 8 , Duane T. Smoot 8 , Sung Ho Jeon 2 , Seon-Young Kim 3,4 and Yong Sun Lee 1 1. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX77555-1072, USA 2. Department of Life Science and Center for Aging and Health Ca...
Source
#1Hyun-Sung Lee (University of Texas MD Anderson Cancer Center)H-Index: 26
#2Kwanbok Lee (UTMB: University of Texas Medical Branch)H-Index: 8
Last. Yong Sun Lee (UTMB: University of Texas Medical Branch)H-Index: 17
view all 11 authors...
// Hyun-Sung Lee 1,2 , Kwanbok Lee 3 , Hee-Jin Jang 1 , Geon Kook Lee 2 , Jong-Lyul Park 4,5 , Seon-Young Kim 4,5 , Sang-Bae Kim 1 , Betty H. Johnson 3 , Jae Ill Zo 6 , Ju-Seog Lee 1,7 , Yong Sun Lee 3 1 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 2 Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, 410-769, Korea 3 Department of Biochemistry and Molecular Biology, The University of Texas Medical B...
Source
Cited By18
Newest
#1Jens C. Hahne (ICR: Institute of Cancer Research)H-Index: 24
#2Andrea Lampis (ICR: Institute of Cancer Research)H-Index: 20
Last. Nicola Valeri (ICR: Institute of Cancer Research)H-Index: 32
view all 3 authors...
Non-coding RNAs are important regulators of differentiation during embryogenesis as well as key players in the fine-tuning of transcription and furthermore, they control the post-transcriptional regulation of mRNAs under physiological conditions. Deregulated expression of non-coding RNAs is often identified as one major contribution in a number of pathological conditions. Non-coding RNAs are a heterogenous group of RNAs and they represent the majority of nuclear transcripts in eukaryotes. An evo...
Source
#1Stephanie Cabarcas-Petroski (PSU: Pennsylvania State University)H-Index: 2
#2Patricio I. Meneses (Fordham University)H-Index: 14
Last. Laura Schramm (St. John's University)H-Index: 17
view all 3 authors...
Deregulation of the RNA polymerase III specific TFIIIB subunit BRF2 occurs in subtypes of human cancers. However, correlations between BRF2 alterations and clinical outcomes in breast cancer are limited. We conducted this review to analyze BRF2 alterations in genomic data sets housed in Oncomine and cBioPortal to identify potential correlations between BRF2 alterations and clinical outcomes. The authors queried both Oncomine and cBioPortal for alterations in BRF2 in human cancers and performed m...
Source
#1Meghdad Yeganeh (UNIL: University of Lausanne)H-Index: 6
#2Nouria Hernandez (UNIL: University of Lausanne)H-Index: 54
RNA polymerase (Pol) III is responsible for transcription of different noncoding genes in eukaryotic cells, whose RNA products have well-defined functions in translation and other biological processes for some, and functions that remain to be defined for others. For all of them, however, new functions are being described. For example, Pol III products have been reported to regulate certain proteins such as protein kinase R (PKR) by direct association, to constitute the source of very short RNAs ...
Source
Nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886′s tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886′s impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival p...
Source
: Protein kinase R (PKR), originally known as an antiviral protein, senses various stresses as well as pathogen-driven double-stranded RNAs. Thereby activated PKR provokes diverse downstream events, including eIF2α phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells activation. Consequently, PKR induces apoptosis and inflammation, both of which are highly important in cancer as much as its original antiviral role. Therefore, cellular proteins and RNAs should tightl...
Source
#2Alberto MesaH-Index: 3
Last. María Ángel GarcíaH-Index: 32
view all 16 authors...
Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer...
Source
#1Guillaume Hummel (UDS: University of Strasbourg)H-Index: 3
#2Jessica M. Warren (CSU: Colorado State University)H-Index: 24
Last. Laurence Drouard (UDS: University of Strasbourg)H-Index: 5
view all 3 authors...
: Transfer RNAs are among the most ancient molecules of life on earth. Beyond their crucial role in protein synthesis as carriers of amino acids, they are also important players in a plethora of other biological processes. Many debates in term of biogenesis, regulation and function persist around these fascinating non-coding RNAs. Our review focuses on the first step of their biogenesis in eukaryotes, i.e. their transcription from nuclear genes. Numerous and complementary ways have emerged durin...
Source
#1John L. Petrie (Ebor: University of York)H-Index: 8
#2Caroline Swan (Ebor: University of York)H-Index: 12
Last. Robert J. White (Ebor: University of York)H-Index: 54
view all 9 authors...
RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. A small molecule pol III inhibitor can cause POLR3G depletion, induce similar differentiation and suppress proliferation and viability of cancer cell...
Source
DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have disc...
Source
Introduction: This review aimed to present common points, intersections and potential interactions or mutual effects for hernia and cancer. Besides direct relationships, indirect connections and possible involvements were searched. Materials and Methods: A systematic search of PubMed database was performed in July 2018 as well as a search of relevant journals and reference lists. The total number of screened articles was 1422. Some articles were found in multiple different searches. A last PubMe...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.