Sprouty keeps bowel kinases regular in colon cancer, while miR-21 targets Sprouty

Frey, Mark R.; Carraro, Gianni; Batra, Raj K.; Polk, D. Brent; Warburton, David

doi:10.4161/cbt.11.1.14176

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…Although it is unclear how miR-21 regulates EMT in ovarian cancer cells, it is possible that miR-21 may directly or indirectly regulate EMT through suppressing the expression of target genes or downstream pathways of these genes. For example, miR-21 was previously reported to target SPRY2 in glioma and colon cancers 20-22. We found that miR-21 also targeted SPRY2 in ovarian cancer cells, which was a negative regulator of ERK1/2 cell survival pathway as shown in Figure 4D.…”

Section: Discussionsupporting

confidence: 52%

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

Huo¹,

Zhao²,

Yin³

et al. 2017

J. Cancer

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CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells.

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Section: Discussionsupporting

confidence: 52%

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

Huo¹,

Zhao²,

Yin³

et al. 2017

J. Cancer

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“…MiR-21 is referred to as an ‘oncomiR' because it downregulates tumor suppressor genes, such as Pdcd4 , phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ), transforming growth factor- β -induced (also known as Big-h3 ), BTG family member 2 ( Btg2 ) and reversion-inducing-cysteine-rich protein with kazal motifs ( Reck ). 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 Our data showed that Tipe2 is a new direct target of miR-21. The identification of miR-21 binding site within Tipe2 coding region instead of 3′-UTR is not surprising because it has been reported that some miRNA species regulate gene expression by targeting coding regions.…”

Section: Discussionmentioning

confidence: 60%

MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2

Ruan

Wang

et al. 2014

Cell Death Dis

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MicroRNAs (MiRs) are short noncoding RNAs that can regulate gene expression. It has been reported that miR-21 suppresses apoptosis in activated T cells, but the molecular mechanism remains undefined. Tumor suppressor Tipe2 (or tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TNFAIP8L2)) is a newly identified anti-inflammatory protein of the TNFAIP8 family that is essential for maintaining immune homeostasis. We report here that miR-21 is a direct target of nuclear factor-κB and could regulate Tipe2 expression in a Tipe2 coding region-dependent manner. In activated T cells and macrophages, Tipe2 expression was markedly downregulated, whereas miR-21 expression was upregulated. Importantly, Tipe2-deficient T cells were significantly less sensitive to apoptosis. Conversely, overexpression of Tipe2 in EL-4 T cells increased their susceptibility to activation-induced apoptosis. Therefore, Tipe2 provides a molecular bridge between miR-21 and cell apoptosis; miR-21 suppresses apoptosis in activated T cells at least in part through directly targeting tumor suppressor gene Tipe2.

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“…The mammalian Sprouty family of signal transduction proteins consists of 4 endogenous regulators that modify downstream cellular responses mediated by RTK activation including epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) . As modulators of MAPK/ERK pathway, Sprouty proteins’ deregulation is reported in development, progression and metastasis of different cancer types such as colon cancer, lung cancer, prostate and breast cancer .…”

Section: The Ras/mapk Pathway In Hepatocarcinomamentioning

confidence: 99%

The Ras/MAPK pathway and hepatocarcinoma: pathogenesis and therapeutic implications

Delire

Stärkel

2015

Eur J Clin Investigation

215

179

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Background Hepatocellular carcinoma (HCC) is still a major health problem, often diagnosed at an advanced stage. The multikinase inhibitor sorafenib is to date the sole approved systemic therapy. Several signalling pathways are implicated in tumour development and progression. Among these pathways, the Ras/MAPK pathway is activated in 50-100% of human HCCs and is correlated with a poor prognosis. The aim of this work was to review the main intracellular mechanisms leading to aberrant Ras pathway activation in HCC and the potential therapeutic implications.

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Sprouty keeps bowel kinases regular in colon cancer, while miR-21 targets Sprouty

Cited by 12 publications

References 26 publications

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor gene Tipe2

The Ras/MAPK pathway and hepatocarcinoma: pathogenesis and therapeutic implications

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