Histone Methyltransferase PR-Set7 and Histone Variant H2A.Z, Induced during Hepatocarcinogenesis, Repress the Promoter Activity of the Tumor Marker Gene and the Ras-Induced Colony Formation Activity

ABSTRACT Studies of the Hepatitis C virus (HCV) replication cycle have been made possible with the development of subgenomic selectable RNAs that replicate autonomously in cultured cells. In these replicons the region encoding the HCV structural proteins was replaced by the neomycin phosphotransferase gene, allowing the selection of transfected cells that support high-level replication of these RNAs. Subsequent analyses revealed that, within selected cells, HCV RNAs had acquired adaptive mutations that increased the efficiency of colony formation by an unknown mechanism. Using a panel of replicons that differed in their degrees of cell culture adaptation, in this study we show that adaptive mutations enhance RNA replication. Transient-transfection assays that did not require selection of transfected cells demonstrated a clear correlation between the level of adaptation and RNA replication. The highest replication level was found with an adapted replicon carrying two amino acid substitutions located in NS3 and one in NS5A that acted synergistically. In contrast, the nonadapted RNA replicated only transiently and at a low level. The correlation between the efficiency of colony formation and RNA replication was corroborated with replicons in which the selectable marker gene was replaced by the gene encoding firefly luciferase. Upon transfection of naive Huh-7 cells, the levels of luciferase activity directly reflected the replication efficiencies of the various replicon RNAs. These results show that cell culture-adaptive mutations enhance HCV RNA replication.

Download Full-text

Study of lung cancer regulatory network that involves erbB4 and tumor marker gene

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2017.01.038 ◽

2017 ◽

Vol 24 (3) ◽

pp. 649-657 ◽

Cited By ~ 2

Author(s):

Xuhui Ma ◽

Lu Li ◽

Tongde Tian ◽

Huaimin Liu ◽

Qiujian Li ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Marker ◽

Regulatory Network ◽

Marker Gene

Download Full-text

Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122

Cancers ◽

10.3390/cancers13102376 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2376

Author(s):

Lan-Ting Yuan ◽

Wei-Jiunn Lee ◽

Yi-Chieh Yang ◽

Bo-Rong Chen ◽

Ching-Yao Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Colony Formation ◽

Disease Free Survival ◽

Histone Methyltransferase ◽

Control Group ◽

Functional Evaluation ◽

Expression Levels ◽

Liver Cancers ◽

Hcc Cells

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers, which is the second most lethal tumor worldwide. Epigenetic deregulation is a common trait observed in HCC. Recently, increasing evidence suggested that the G9a histone methyltransferase might be a novel regulator of HCC development. However, several HCC cell lines were recently noted to have HeLa cell contamination or to have been derived from non-hepatocellular origin, suggesting that functional validation of G9a in proper HCC models is still required. Herein, we first confirmed that higher G9a messenger RNA and protein expression levels were correlated with poor overall survival (OS) and disease-free survival (DFS) rates of HCC patients from The Cancer Genome Atlas (TCGA) dataset and our recruited HCC cohort. In an in vitro functional evaluation of HCC cells, HCC36 (hepatitis B virus-positive (HBV+) and Mahlavu (HBV−)) cells showed that G9a participated in promoting cell proliferation, colony formation, and migration/invasion abilities. Moreover, orthotopic inoculation of G9a-depleted Mahlavu cells in NOD-SCID mice also resulted in a significantly decreased tumor burden compared to the control group. Furthermore, after surveying microRNA (miRNA; miR) prediction databases, we identified the liver-specific miR-122 as a G9a-targeting miRNA. In various HCC cell lines, we observed that miR-122 expression levels tended to be inversely correlated to G9a expression levels. In clinical HCC specimens, a significant inverse correlation of miR-122 and G9a mRNA expression levels was also observed. Functionally, the colony formation and invasive ability were attenuated in miR-122-overexpressing HCC cells. HCC patients with low miR-122 and high G9a expression levels had the worst OS and DFS rates compared to others. Together, our results confirmed the importance of altered G9a expression during HCC progression and discovered that a novel liver-specific miR-122-G9a regulatory axis exists.

Download Full-text

Identification of an Embryonic Cell-Specific Region within the Pineapple SERK1 Promoter

Genes ◽

10.3390/genes10110883 ◽

2019 ◽

Vol 10 (11) ◽

pp. 883 ◽

Cited By ~ 1

Author(s):

Luan ◽

He ◽

Xie ◽

Chen ◽

Mao ◽

...

Keyword(s):

Somatic Embryogenesis ◽

Transcription Initiation ◽

Promoter Activity ◽

Specific Activity ◽

Marker Gene ◽

Immature Embryo ◽

Embryonic Cell ◽

Regulatory Sequence ◽

Regulatory Sequences ◽

Embryonic Callus

Plant tissue culture methods, such as somatic embryogenesis, are attractive alternatives to traditional breeding methods for plant propagation. However, they often suffer from limited efficiency. Somatic embryogenesis receptor kinase (SERK)1 is a marker gene of early somatic embryogenesis in several plants, including pineapple. It can be selectively induced and promotes a key step in somatic embryogenesis. We investigated the embryonic cell-specific transcriptional regulation of AcSERK1 by constructing a series of vectors carrying the GUS（Beta-glucuronidase） reporter gene under the control of different candidate cis-regulatory sequences. These vectors were transfected into both embryonic and non-embryonic callus, and three immature embryo stages and the embryonic-specific activity of the promoter fragments was analyzed. We found that the activity of the regulatory sequence of AcSERK1 lacking −983 nt ~−880 nt, which included the transcription initiation site, was significantly reduced in the embryonic callus of pineapple, accompanied by the loss of embryonic cell-specific promoter activity. Thus, this fragment is an essential functional segment with highly specific promoter activity for embryonic cells, and it is active only from the early stages of somatic embryo development to the globular embryo stage. This study lays the foundation for identifying mechanisms that enhance the efficiency of somatic embryogenesis in pineapple and other plants.

Download Full-text

A Modified Ant Colony Optimization Algorithm for Tumor Marker Gene Selection

Genomics Proteomics & Bioinformatics ◽

10.1016/s1672-0229(08)60050-9 ◽

2009 ◽

Vol 7 (4) ◽

pp. 200-208 ◽

Cited By ~ 43

Author(s):

Hualong Yu ◽

Guochang Gu ◽

Haibo Liu ◽

Jing Shen ◽

Jing Zhao

Keyword(s):

Tumor Marker ◽

Ant Colony Optimization ◽

Optimization Algorithm ◽

Gene Selection ◽

Marker Gene ◽

Ant Colony ◽

Ant Colony Optimization Algorithm

Download Full-text

Anti-inflammatory dihydroxanthones from a Diaporthe species

Biological Chemistry ◽

10.1515/hsz-2021-0192 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Markus Rohr ◽

Anna Maria Kiefer ◽

Ulrich Kauhl ◽

Jonathan Groß ◽

Till Opatz ◽

...

Keyword(s):

Density Functional ◽

Promoter Activity ◽

Inflammatory Marker ◽

Marker Gene ◽

Mrna Levels ◽

Dependent Manner ◽

Cytokines And Chemokines ◽

Anti Inflammatory ◽

Inducible Protein ◽

Nfκb Pathway

Abstract In a search for anti-inflammatory compounds from fungi inhibiting the promoter activity of the small chemokine CXCL10 (Interferon-inducible protein 10, IP-10) as a pro-inflammatory marker gene, the new dihydroxanthone methyl (1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) and the previously described dihydroxanthone AGI-B4 (1) were isolated from fermentations of a Diaporthe species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy, mass spectrometry, and calculations using density functional theory (DFT). Compounds 1 and 2 inhibited the LPS/IFNγ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 4.1 µM (±0.2 µM) and 1.0 µM (±0.06 µM) respectively. Moreover, compounds 1 and 2 reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFNγ stimulated MonoMac6 cells by interfering with the Stat1 and NFκB pathway.

Download Full-text