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

Cartier, F; Indersie, Emilie; Lesjean, Sarah; Charpentier, Justine; Hooks, Katarzyna B.; Ghousein, Amani; Desplat, Angélique; Dugot‐Senant, Nathalie; Trezeguet, Véronique; Sagliocco, Francis; Hagedorn, Martin; Grosset, Christophe

doi:10.18632/oncotarget.17162

Cited by 38 publications

(40 citation statements)

References 46 publications

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“…miR-203a-3p in liver cancer and bladder cancer was up-regulated [33, 34], and the expression of other miR-203 family members could be up-regulated in cervical cells [35]. Other studies have shown that the expression of miR-203a-3p was down-regulated in nasopharyngeal carcinoma [23].…”

Section: Discussionmentioning

confidence: 99%

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

Xiao

Chen

et al. 2018

Cell Physiol Biochem

134

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Background/Aims: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). Methods: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. Results: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/β-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/β-catenin signaling inhibition induced by HOTAIR knockdown. Conclusions: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

Xiao

Chen

et al. 2018

Cell Physiol Biochem

134

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“…Primer efficiency was between 95% and 105%. miR-4510 expression was measured as described before [2].…”

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confidence: 99%

“…Total RNA was extracted from cultured cells using Trizol (Sigma, St Louis, MO, USA) reagent or mirVana miRNA Isolation Kit (Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions. miR-4510 expression was measured as described previously[2]. To quantify mRNA expression, complementary DNA was synthesized with the Maxima Reverse Transcriptase kit (Thermo…”

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confidence: 99%

miR‐4510 blocks hepatocellular carcinoma development through RAF1 targeting and RAS/RAF/MEK/ERK signalling inactivation

Ghousein

Mosca

Cartier

et al. 2019

Liver International

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BackgroundTherapeutic outcomes using the multikinase inhibitors, sorafenib and regorafenib, remain unsatisfactory for patients with advanced hepatocellular carcinoma (HCC). Thus, new drug modalities are needed. We recently reported the remarkable capacity of miR‐4510 to impede the growth of HCC and hepatoblastoma through Glypican‐3 (GPC3) targeting and Wnt pathway inactivation.MethodsTo identify new targets of miR‐4510, we used a label‐free proteomic approach and reported down‐regulation of RAF proto‐oncogene serine/threonine‐protein kinase (RAF1) by miR‐4510. Because the tumourigenic role of RAF1 in HCC is controversial, we further studied RAF1:miR‐4510 interactions using cellular, molecular as well as functional approaches and a chicken chorioallantoic membrane (CAM) xenograft model.ResultsWe found an increase in RAF1 protein in 59.3% of HCC patients and a specific up‐regulation of its transcript in proliferative tumours. We showed that miR‐4510 inactivates the RAS/RAF/MEK/ERK pathway and reduces the expression of downstream targets (ie c‐Fos proto‐oncogene [FOS]) through RAF1 direct targeting. At a cellular level, miR‐4510 inhibited HCC cell proliferation and migration and induced senescence in part by lowering RAF1 messenger RNA (mRNA) and protein expression. Finally, we confirmed the pro‐tumoural function of RAF1 protein in HCC cells and its ability to sustain HCC tumour progression in vitro and in vivo.ConclusionsIn this work, we confirm that RAF1 acts as an oncogene in HCC and further demonstrate that miR‐4510 acts as a strong tumour suppressor in the liver by targeting many proto‐oncogenes, including GPC3 and RAF1, and subsequently controlling key biological and signalling pathways among which Wnt and RAS/RAF/MEK/ERK signals.

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“…To our knowledge, only one report about miR‐4510 function has been found. This finding identifies miR‐4510 as a suppressor in liver cancer by targeting glypican‐3 (Cartier et al, 2017). Conformably, our results suggested that miR‐4510 served as a suppressor in GIST cells.…”

Section: Discussionmentioning

confidence: 97%

miR‐4510 acts as a tumor suppressor in gastrointestinal stromal tumor by targeting APOC2

Chen

Qin

Cui

et al. 2020

Journal Cellular Physiology

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Dysregulation of microRNAs (miRNAs) expression has been demonstrated in gastrointestinal stromal tumor (GIST). In this study, we aimed to determine the differential miRNAs expression in GISTs and explore the functional mechanism of differential miRNAs in GIST cells. We measured differential miRNAs in six pairs of GIST tissues and matched adjacent tissues through a high‐throughput sequencing, which was confirmed in 64 pairs of GIST tissues and adjacent tissues by real‐time polymerase chain reaction. We found that miR‐4510 expression was significantly downregulated in GIST tissues compared to matched control tissues. Luciferase reporter assay identified apolipoprotein C‐II (APOC2) as a direct target of miR‐4510. Overexpression of miR‐4510 inhibited the mRNA and protein expression of APOC2. In addition, overexpression of miR‐4510 suppressed GIST cell proliferation, migration, and invasion. Overexpression of miR‐4510 also inhibited the phosphorylation of AKT and ERK1/2, reduced the expression of matrix metallopeptidase 2 (MMP2) and MMP9. APOC2 knockdown mimicked the effect of miR‐4510 overexpression. Further investigation confirmed that APOC2 was notably upregulated in GIST tissues compared to adjacent control tissues. These results suggested that miR‐4510 downregulation could promote GIST progression, including growth, invasion, and metastasis, through increasing APOC2 expression.

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

Cited by 38 publications

References 46 publications

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

miR‐4510 blocks hepatocellular carcinoma development through RAF1 targeting and RAS/RAF/MEK/ERK signalling inactivation

miR‐4510 acts as a tumor suppressor in gastrointestinal stromal tumor by targeting APOC2

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