Upregulation of AUF1 is involved in the proliferation of esophageal squamous cell carcinoma through GCH1

Gao, Yi; Wang, Wenjie; Cao, Jinming; Wang, Fangjun; Geng, Yangyang; Cao, Jianping; Xu, Xiaohui; Zhou, Jundong; Liu, Pengfei; Zhang, Shuyu

doi:10.3892/ijo.2016.3713

Cited by 29 publications

(40 citation statements)

References 31 publications

(37 reference statements)

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“…This RNA-binding protein regulates the expression of a rich array of proteins, many of which are the key players in cell cycle, apoptosis, and inflammation [ 42 , 43 ]. Studies have demonstrated that AUF1 shows both pro- and anti-apoptotic activity [ 35 , 44 , 45 ]. In this study, although we did not observe increased ratio of cells in the early phase of apoptosis when the expression of AUF1 was knocked down by specific siRNA, the proportion of cells in late apoptosis and necrosis was indeed elevated, indicating that AUF1 might play a role in the survival of HCC cells.…”

Section: Discussionmentioning

confidence: 99%

RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1 in hepatocellular carcinoma

Yang

Huang

et al. 2018

Oncotarget

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Hepatocellular carcinoma (HCC) is one of the common cancers worldwide, especially in developing countries. Although the chronic infections of hepatitis B and C viruses have been established as the etiological factors of HCC, the mechanism for the tumorigenesis and development of HCC is still unclear. The liver-specific microRNA-122 (miR-122), an established tumor-suppressor miRNA, is often down-regulated in HCC, while the underlying mechanism is not well understood. Here we report that the AU-rich element-binding factor AUF1 suppresses the expression of Dicer1, the type III RNase that is required for microRNA maturation, leading to the inhibited biogenesis of miR-122. Overexpression of AUF1 led to the decreased expression of Dicer1 and miR-122, while the level of the miR-122 precursor (pre-miR-122) was increased. On the other hand, siRNA of AUF1 (siAUF1) increased the levels of Dicer1 mRNA and miR-122, but it reduced the abundance of pre-miR-122. Consistent with the reported data, this study demonstrated that AUF1 and Dicer1 showed opposite expression pattern in both human HCC tissues and cell lines. In addition, AUF1 inhibited the expression of Dicer1 by interacting with the 3′ untranslated region (3′UTR) and coding region of DICER1 mRNA. Moreover, the knockdown of AUF1 by siRNA altered the expression of other miRNAs and promoted HCC cell death. In conclusion, AUF1 down-regulates the expression miR-122 by interacting with the 3′UTR and coding region of DICER1 mRNA and suppressing Dicer1 expression. The AUF1/Dicer1/miR-122 pathway might play a critical role in the development of HCC.

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Section: Discussionmentioning

confidence: 99%

RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1 in hepatocellular carcinoma

Yang

Huang

et al. 2018

Oncotarget

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“…The hnRNP D, that is overexpression in Eca-109 esophageal cancer cell line, has been recognized to bind the 3 -UTR AUrich motifs of GTP cyclohydrolase (GCH1) transcripts causing GCH1 overexpression and enhanced cell proliferation and colony formation (Gao et al, 2016). Moreover, the hnRNP D protein can specifically bind to single-stranded d(TTAGGG)n human telomeric repeats through its C-terminal binding domain (BD2), thus impeding the formation of a DNA-quadruplex while favoring telomeres elongation and maintenance (Enokizono et al, 2005).…”

Section: Oncogenic Functions Of Hnrnps and Srsfsmentioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

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The spliceosomal complex components, together with the heterogeneous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich (SR) proteins, regulate the process of constitutive and alternative splicing, the latter leading to the production of mRNA isoforms coding multiple proteins from a single pre-mRNA molecule. The expression of splicing factors is frequently deregulated in different cancer types causing the generation of oncogenic proteins involved in cancer hallmarks. Cervical cancer is caused by persistent infection with oncogenic human papillomaviruses (HPVs) and constitutive expression of viral oncogenes. The aberrant activity of hnRNPs and SR proteins in cervical neoplasia has been shown to trigger the production of oncoproteins through the processing of pre-mRNA transcripts either derived from human genes or HPV genomes. Indeed, hnRNP and SR splicing factors have been shown to regulate the production of viral oncoprotein isoforms necessary for the completion of viral life cycle and for cell transformation. Target-therapy strategies against hnRNPs and SR proteins, causing simultaneous reduction of oncogenic factors and inhibition of HPV replication, are under development. In this review, we describe the current knowledge of the functional link between RNA splicing factors and deregulated cellular as well as viral RNA maturation in cervical cancer and the opportunity of new therapeutic strategies.

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“… CCH1 , which is a voltage-gated high-affinity calcium channel with several homologs that were UES, including: CACNA1A , underexpressed in breast, colorectal, esophageal, gastric, and brain cancers; CACNA1B , underexpressed in breast and brain cancers; CACNA1C , underexpressed in brain, bladder, lung, lymphoma, prostate, and renal cancers; CACNA1E , underexpressed in breast, brain, gastric, leukemia, lung, and prostate cancers; and CACNA1F , underexpressed in lymphoma [274] ; IZH1 , a yeast membrane protein involved in zinc ion homeostasis, having a human homolog, PAQR1/ADIPOR1 that encodes the adiponectin receptor protein 1, which is differentially regulated in breast cancers [278,279] ; FAT1 , a yeast fatty acid transporter and very long-chain fatty acyl-CoA synthetase that corresponds to SLC27A2 (very long-chain acyl Co-A synthetase), which is underexpressed in lung cancer [275], and SLC27A3 (long-chain fatty acid transport), which is hypermethylated in melanoma [276]; FOL2/GCH1 , a GTP-cyclohydrolase that catalyzes the first step in folic acid biosynthesis. Downregulation of GCH1 occurs in esophageal squamous cell carcinoma [277]. …”

Section: Resultsmentioning

confidence: 99%

“…FOL2/GCH1 , a GTP-cyclohydrolase that catalyzes the first step in folic acid biosynthesis. Downregulation of GCH1 occurs in esophageal squamous cell carcinoma [277].…”

Section: Resultsmentioning

confidence: 99%

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Santos

Icyuz

Pound

et al. 2019

Preprint

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10Knowledge about synthetic lethality can be applied to enhance the efficacy of 11 anti-cancer therapies in individual patients harboring genetic alterations in their cancer 12 that specifically render it vulnerable. We investigated the potential for high-resolution 13 phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, 14 comprehensive, and quantitative assessment of drug-gene interaction for gemcitabine 15 and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures 16 yet distinct anti-tumor efficacy. Human deoxycytidine kinase (dCK) was conditionally 17 expressed in the S. cerevisiae genomic library of knockout and knockdown (YKO/KD) 18 strains, to globally and quantitatively characterize differential drug-gene interaction for 19 gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, 20 histone modification, chromatin remodeling, and apoptosis-related processes influence 21 gemcitabine specifically, while drug-gene interaction specific to cytarabine was less 22 enriched in Gene Ontology. Processes having influence over both drugs were DNA 23 repair and integrity checkpoints and vesicle transport and fusion. Non-GO-enriched 24 genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics 25 data were integrated to identify yeast-human homologs with correlated differential gene 26 2 expression and drug-efficacy, thus providing a unique resource to predict whether 27 differential gene expression observed in cancer genetic profiles are causal in tumor-28 specific responses to cytotoxic agents. 29 30 Keywords: 31 yeast phenomics, gene-drug interaction, genetic buffering, quantitative high 32 throughput cell array phenotyping (Q-HTCP), cell proliferation parameters (CPPs), 33 gemcitabine, cytarabine, recursive expectation-maximization clustering (REMc), 34 pharmacogenomics 35 36 Introduction: 37Genomics has enabled targeted therapy aimed at cancer driver genes and 38 oncogenic addiction [1], yet traditional cytotoxic chemotherapeutic agents remain among 39 the most widely used and efficacious anti-cancer therapies [2]. Changes in the genetic 40 network underlying cancer can produce vulnerabilities to cytotoxic chemotherapy that 41 further influence the therapeutic window and provide additional insight into their 42 mechanisms of action [3,4]. A potential advantage of so-called synthetic lethality-based 43 treatment strategies is that they could have efficacy against passenger gene mutation or 44 compensatory gene expression, while classic targeted therapies are directed primarily at 45 driver genes ( Fig. 1A). Quantitative high throughput cell array phenotyping of the yeast 46 knockout and knockdown libraries provides a phenomic means for systems level, high- 47resolution modeling of gene interaction [5][6][7][8][9], which is applied here to predict cancer-48 relevant drug-gene interaction through integration with cancer pharmacogenomics 49 resources ( Fig. 1B). 50Nucleoside analogs include a diverse group of co...

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Upregulation of AUF1 is involved in the proliferation of esophageal squamous cell carcinoma through GCH1

Cited by 29 publications

References 31 publications

RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1 in hepatocellular carcinoma

RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1 in hepatocellular carcinoma

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

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