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      Long noncoding RNA LINC01234 promotes serine hydroxymethyltransferase 2 expression and proliferation by competitively binding miR-642a-5p in colon cancer

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          Abstract

          Long noncoding RNAs (lncRNAs) have been indicated as important regulators in various human cancers. However, the overall biological roles and clinical significance of most lncRNAs in colon carcinogenesis are not fully understood. Hence, we investigated the clinical significance, biological function and mechanism of LINC01234 in colon cancer. First, we analyzed LINC01234 alterations in colon cancer tissues and corresponding paracancerous tissues through the analysis of sequencing data obtained from The Cancer Genome Atlas and colon cancer patients. Next, we evaluated the effect of LINC01234 on colon cancer cell proliferation and its regulatory mechanism of serine hydroxymethyltransferase 2 (SHMT2) by acting as a competing endogenous RNA (ceRNA). We found that LINC01234 expression was significantly upregulated in colon cancer tissues and was associated with a shorter survival time. Furthermore, the knockdown of LINC01234 induced proliferation arrest via suppressing serine/glycine metabolism. Mechanistic investigations have indicated that LINC01234 functions as a ceRNA for miR-642a-5p, thereby leading to the derepression of its endogenous target serine hydroxymethyltransferase 2 (SHMT2). LINC01234 is significantly overexpressed in colon cancer, and the LINC01234–miR642a-5p–SHMT2 axis plays a critical role in colon cancer proliferation. Our findings may provide a potential new target for colon cancer diagnosis and therapy.

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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            Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

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              The metabolic syndrome: A high-risk state for cancer?

              The metabolic syndrome is composed of cardiovascular risk factors including increased body mass index/waist circumference, blood pressure, plasma glucose, and triglycerides, as well as decreased high-density lipoprotein cholesterol. The essence of the metabolic syndrome lies in the clustering of these risk factors, which are associated with cardiovascular disease. Interestingly, most of the components of the metabolic syndrome have individually been linked in some way to the development of cancer. However, epidemiological studies linking the metabolic syndrome to cancer are scarce. Nevertheless, two such studies indicate that the clustering of metabolic syndrome components significantly increases the risk of colon cancer mortality compared with the individual components. The purpose of this review is to further explore the potential relationship between the metabolic syndrome and cancer risk. Specifically, we examine the hypothesis that individual components of the metabolic syndrome contribute to the development of several processes, including insulin resistance, aromatase activity, adipokine production, angiogenesis, glucose utilization, and oxidative stress/DNA damage, which can work together to increase cancer risk beyond that of the individual components alone. We propose that the metabolic syndrome be considered as a high-risk state for certain types of cancer and that this relationship should be systematically explored across cancer types.
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                Author and article information

                Contributors
                pengjiuz@126.com
                Journal
                Cell Death Dis
                Cell Death Dis
                Cell Death & Disease
                Nature Publishing Group UK (London )
                2041-4889
                12 February 2019
                12 February 2019
                February 2019
                : 10
                : 2
                : 137
                Affiliations
                [1 ]GRID grid.431010.7, Department of Gastrointestinal surgery, , The Third XiangYa Hospital of Central South University, ; Changsha, Hunan 410013 China
                [2 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, College of Life Sciences, , Central South University, ; Changsha, Hunan 410078 China
                [3 ]GRID grid.413389.4, Department of General Surgery, , Affiliated Hospital of Xuzhou Medical University, ; 221000 Changsha, China
                [4 ]Department of Otolaryngology-Head Neck Surgery, The Fourth Hospital of Changsha (The Changsha Affiliated Hospital of Hunan Normal University), Hunan Normal University, Changsha, Hunan 410013 China
                Article
                1352
                10.1038/s41419-019-1352-4
                6372696
                30755591
                13d6f6bd-2826-4915-a2a4-d7da53cb731b
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 September 2018
                : 26 December 2018
                : 7 January 2019
                Funding
                Funded by: This work was supported by National Nature Science Foundation of China (No. 81773130; No. 81602568).
                Categories
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                © The Author(s) 2019

                Cell biology
                Cell biology

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