Analysis of post-transcriptional regulation using the FunREG method

Laloo, Benoît; Maurel, M.; Jalvy-Delvaille, Sandra; Sagliocco, Francis; Grosset, Christophe

doi:10.1042/bst0381608

Cited by 7 publications

(10 citation statements)

References 37 publications

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“…To assess the relevance of this site, two point mutations (r.311C>G and r.313C>G) were inserted in this 3’-UTR sequence. Then FunREG analysis was performed [25, 26]. As expected, miR-4510 decreased the fluorescence of GFP with a wild-type GPC3 3’-UTR (Figure 7B) demonstrating its ability to regulate GPC3 at a post-transcriptional level.…”

Section: Resultsmentioning

confidence: 80%

New tumor suppressor microRNAs target glypican-3 in human liver cancer

et al. 2017

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Glypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral compared to non-tumoral liver and inhibited tumor cell proliferation. Interestingly, miR-4510 inversely correlated with GPC3 mRNA and protein in HCC samples. This microRNA also induced apoptosis of hepatoma cells and blocked tumor growth in vivo in the chick chorioallantoic membrane model. We further show that the tumor suppressive effect of miR-4510 is mediated through direct targeting of GPC3 mRNA and inactivation of Wnt/β-catenin transcriptional activity and signaling pathway. Moreover, miR-4510 up-regulated the expression of several tumor suppressor genes while reducing the expression of other pro-oncogenes. In summary, we uncovered several new microRNAs targeting the oncogenic functions of GPC3. We provided strong molecular, cellular and in vivo evidences for the tumor suppressive activities of miR-4510 bringing to the fore the potential value of this microRNA in HCC therapy.

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Section: Resultsmentioning

confidence: 80%

New tumor suppressor microRNAs target glypican-3 in human liver cancer

et al. 2017

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“…Three days later, eGFP protein (P) and mRNA (M) expression levels were determined using FACS and RT-qPCR, respectively. Finally P/ TCN, M/TCN, and P/M ratios, which, respectively, correspond to the global post-transcriptional regulation, the mRNA stability, and the translation efficiency, were calculated (Laloo et al 2009(Laloo et al , 2010. As previously reported (Maurel et al 2013), FunREG ratios ( Fig.…”

Section: Mir-1291 Targets An Intermediate Factor That Regulates Gpc3 mentioning

confidence: 83%

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Maurel

Dejeans

Taouji

et al. 2013

RNA

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MicroRNAs (miRNA) are generally described as negative regulators of gene expression. However, some evidence suggests that they may also play positive roles. As such, we reported that miR-1291 leads to a GPC3 mRNA expression increase in hepatoma cells through a 3 ′ untranslated region (UTR)-dependent mechanism. In the absence of any direct interaction between miR-1291 and GPC3 mRNA, we hypothesized that miR-1291 could act by silencing a negative regulator of GPC3 mRNA expression. Based on in silico predictions and experimental validation, we demonstrate herein that miR-1291 represses the expression of the mRNA encoding the endoplasmic reticulum (ER)-resident stress sensor IRE1α by interacting with a specific site located in the 5 ′ UTR. Moreover, we show, in vitro and in cultured cells, that IRE1α cleaves GPC3 mRNA at a 3 ′ UTR consensus site independently of ER stress, thereby prompting GPC3 mRNA degradation. Finally, we show that the expression of a miR-1291-resistant form of IRE1α abrogates the positive effects of miR-1291 on GPC3 mRNA expression. Collectively, our data demonstrate that miR-1291 is a biologically relevant regulator of GPC3 expression in hepatoma cells and acts through silencing of the ER stress sensor IRE1α.

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“…The reason is that individually controlled transcripts also differ in their fate (storage, degradation or translation) and, in case of storage and translation, storage period and translation speed, respectively. Furthermore, biological significance of differential regulation of transcripts may be even greater, being linked to disease (Trombetta-Lima et al , 2015) or miRNA or other processing control mechanisms (Laloo et al. , 2010).…”

Section: Discussionmentioning

confidence: 99%

Individual expression features of GPX2, NQO1 and SQSTM1 transcript variants induced by hydrogen peroxide treatment in HeLa cells

et al. 2017

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Pathway activity assessment-based approaches are becoming highly influential in various fields of biology and medicine. However, these approaches mostly rely on analysis of mRNA expression, and total mRNA from a given locus is measured in the majority of cases. Notably, a significant portion of protein-coding genes produces more than one transcript. This biological fact is responsible for significant noise when changes in total mRNA transcription of a single gene are analyzed. The NFE2L2/AP-1 pathway is an attractive target for biomedical applications. To date, there is a lack of data regarding the agreement in expression of even classical target genes of this pathway. In the present paper we analyzed whether transcript variants of GPX2, NQO1 and SQSTM1 were characterized by individual features of expression when HeLa cells were exposed to pro-oxidative stimulation with hydrogen peroxide. We found that all the transcripts (10 in total) appeared to be significantly individually regulated under the conditions tested. We conclude that individual transcripts, rather than total mRNA, are best markers of pathway activation. We also discuss here some biological roles of individual transcript regulation.

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Analysis of post-transcriptional regulation using the FunREG method

Cited by 7 publications

References 37 publications

New tumor suppressor microRNAs target glypican-3 in human liver cancer

New tumor suppressor microRNAs target glypican-3 in human liver cancer

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Individual expression features of GPX2, NQO1 and SQSTM1 transcript variants induced by hydrogen peroxide treatment in HeLa cells

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