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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      KIAA1429 regulates the migration and invasion of hepatocellular carcinoma by altering m6A modification of ID2 mRNA

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          Abstract

          Purpose

          N6-methyladenosine (m6A), the most abundant mRNA modification in mammals, is involved in various biological processes. KIAA1429 is an important methyltransferase participating in m6A modification. However, the role of KIAA1429 in hepatocellular carcinoma (HCC) is still not well understood. Here, we aimed to investigate the function of KIAA1429 and its corresponding regulation mechanisms in HCC.

          Patients and methods

          HCC-related genes were analyzed by clinical and expression data of HCC patients in The Cancer Genome Atlas (TCGA) database. Expression of KIAA1429 was verified by quantitative reverse-transcription PCR, and interference efficiency was obtained using small interfering RNA (siRNA). Cell proliferation, migration, and invasion were assessed by cell counting kit-8 and transwell assays, and the m6A modification was detected by methylated RNA immunoprecipitation-PCR (MeRIP-PCR).

          Results

          We found a difference in the expression of KIAA1429 between HCC and normal hepatic tissues by analyzing data from the TCGA database. Comparing HCC cell lines (HepG2, Huh-7, HepG2.2.15) with normal hepatic cells (HL-7702), we observed an identically significant difference in KIAA1429 expression. KIAA1429 significantly enhanced proliferation, migration, and invasion of HepG2 cells. Moreover, Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and correlation analysis revealed a significant negative correlation between KIAA1429 and ID2. In the subsequent MeRIP-PCR assay, downregulation of KIAA1429 inhibited m6A modification of ID2 mRNA.

          Conclusion

          KIAA1429 facilitated migration and invasion of HCC by inhibiting ID2 via upregulating m6A modification of ID2 mRNA.

          Most cited references14

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          Molecular pathogenesis of human hepatocellular carcinoma.

          Hepatocarcinogenesis is a slow process during which genomic changes progressively alter the hepatocellular phenotype to produce cellular intermediates that evolve into hepatocellular carcinoma. During the long preneoplastic stage, in which the liver is often the site of chronic hepatitis, cirrhosis, or both, hepatocyte cycling is accelerated by upregulation of mitogenic pathways, in part through epigenetic mechanisms. This leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomere erosion and telomerase re-expression, sometimes microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and emergence of hepatocellular carcinoma are associated with the accumulation of irreversible structural alterations in genes and chromosomes, but the genomic basis of the malignant phenotype is heterogeneous. The malignant hepatocyte phenotype may be produced by the disruption of a number of genes that function in different regulatory pathways, producing several molecular variants of hepatocellular carcinoma. New strategies should enable these variants to be characterized.
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            Epidemiology of primary liver cancer.

            Liver cancer (LC) ranks fifth in frequency in the world with an estimated number of 437,000 new cases in 1990. In developing countries, incidence rates are two- to three-fold higher than in developed countries. The geographic areas at highest risk are located in Eastern Asia, with age-adjusted incidence rates (AAIRs) ranking from 27.6 to 36.6 per 100,000 in men; Middle Africa, with AAIRs ranking from 20.8 to 38.1 per 100,000 in men; and some countries of Western Africa, with AAIRs ranking from 30 to 48 per 100,000 in men. The geographic areas at lowest LC risk are Northern Europe, Australia, New Zealand, and the Caucasian populations in North and Latin America, with AAIRs below 5.0 per 100,000 in men. Excess of LC incidence among men compared to women is universal, with sex ratios between 1.5 and 3.0. Significant variations in LC incidence among different ethnic groups living in the same geographical area and among migrants of the same ethnic groups living in different areas have been extensively described. The variability of LC incidence rates between countries and within countries, strongly suggests differences in exposure to risk factors. The role of chronic infection with the Hepatitis B and hepatitis C viruses (HBV and HCV) in the etiology of LC is well established. The attributable risk estimates for LC for each of these hepatotropic viruses vary among countries but the combined effects of persistent HBV or HCV infections account for well over 80% of LC cases worldwide. Other documented risk factors such as aflatoxin exposure in diets, cigarette smoking, alcohol consumption, and oral contraceptives may explain the residual variation between and within countries. Interactions between some risk factors have been postulated, and are subject of active research. New laboratory techniques and biological markers such as polymerase chain reaction detection of HBV DNA and HCV RNA, as well as specific mutations related to aflatoxin exposure may help to provide quantitative estimates of the risk related to each these factors.
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              The ID proteins: master regulators of cancer stem cells and tumour aggressiveness.

              Inhibitor of DNA binding (ID) proteins are transcriptional regulators that control the timing of cell fate determination and differentiation in stem and progenitor cells during normal development and adult life. ID genes are frequently deregulated in many types of human neoplasms, and they endow cancer cells with biological features that are hijacked from normal stem cells. The ability of ID proteins to function as central 'hubs' for the coordination of multiple cancer hallmarks has established these transcriptional regulators as therapeutic targets and biomarkers in specific types of human tumours.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2019
                07 May 2019
                : 12
                : 3421-3428
                Affiliations
                [1 ]Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, JiangXi, China
                [2 ]Department of Endocrinology, Shangrao People’s Hospital, Shangrao, JiangXi, China, guanjunyu8866@ 123456163.com
                Author notes
                Correspondence: Guanjun Huang, Department of Endocrinology, The People’s Hospital, No 84 of Shuyuan Road, Xinzhou Area, Shangrao, JiangXi, China, Tel +86 139 0703 8882, Email guanjunyu8866@ 123456163.com
                Article
                ott-12-3421
                10.2147/OTT.S180954
                6510231
                31118692
                44b73154-8fd4-462d-ba1d-ef1a2ce7b74f
                © 2019 Cheng et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                n6-methyladenosine,methyltransferases,tumor metastasis,invasion
                Oncology & Radiotherapy
                n6-methyladenosine, methyltransferases, tumor metastasis, invasion

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