miR-21 promotes EGF-induced pancreatic cancer cell proliferation by targeting Spry2

Zhao, Qiuyan; Sumin, Chen; Zhu, Zhongqi; Yu, Lanting; Ren, Yingchun; Jiang, Mier; Weng, Junyong; Li, Baiwen

doi:10.1038/s41419-018-1182-9

Cited by 75 publications

(61 citation statements)

References 43 publications

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“…Dual‐specificity tyrosine phosphorylation‐regulated kinase 1A, which is highly expressed in pancreatic ductal adenocarcinoma, stabilizes c‐Met through Sprouty2 phosphorylation, thereby resulting in the promotion of tumor growth . In pancreatic cancer cells, miR‐21 targets Sprouty2 for promoting EGF‐induced cell proliferation . Sprouty4 does not affect β‐cell carcinogenesis in mice, although it regulates endocrine pancreas development …”

Section: Roles Of Sprouty/spred During Tumorigenesis and Metastasismentioning

confidence: 99%

The Sprouty/Spred family as tumor suppressors: Coming of age

Kawazoe

Taniguchi

2019

Cancer Science

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The Ras/Raf/ERK pathway is one of the most frequently dysregulated signaling pathways in various cancers. In some such cancers, Ras and Raf are hotspots for mutations, which cause continuous activation of this pathway. However, in some other cancers, it is known that negative regulators of the Ras/Raf/ERK pathway are responsible for uncontrolled activation. The Sprouty/Spred family is broadly recognized as important negative regulators of the Ras/Raf/ERK pathway, and its expression is downregulated in many malignancies, leading to hyperactivation of the Ras/Raf/ERK pathway. After the discovery of this family, intensive research investigated the mechanism by which it suppresses the Ras/Raf/ERK pathway and its roles in developmental and pathophysiological processes. In this review, we discuss the complicated roles of the Sprouty/Spred family in tumor initiation, promotion, and progression and its future therapeutic potential.

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Section: Roles Of Sprouty/spred During Tumorigenesis and Metastasismentioning

confidence: 99%

The Sprouty/Spred family as tumor suppressors: Coming of age

Kawazoe

Taniguchi

2019

Cancer Science

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“…Furthermore, miR-21 is involved in the MAPK signalling pathway, which is important for the progression of pancreatic intraepithelial neoplasia (PanIN [ 45 ]). Overexpression of miR-21 has been shown to moderate cell proliferation and apoptosis of PDAC cells through the inhibition of both MAPK/ERK and PI3K/AKT signalling pathways [ 46 ]. Expression of miR-21 is also associated with the TGF-β signalling pathway, which is dysregulated in 80% of PDAC cases [ 47 , 48 ].…”

Section: Introductionmentioning

confidence: 99%

Peptidylarginine Deiminase Inhibitor Application, Using Cl-Amidine, PAD2, PAD3 and PAD4 Isozyme-Specific Inhibitors in Pancreatic Cancer Cells, Reveals Roles for PAD2 and PAD3 in Cancer Invasion and Modulation of Extracellular Vesicle Signatures

Uysal-Onganer

D’Alessio

Mortoglou

et al. 2021

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with limited survival rate. Roles for peptidylarginine deiminases (PADs) have been studied in relation to a range of cancers with roles in epigenetic regulation (including histone modification and microRNA regulation), cancer invasion, and extracellular vesicle (EV) release. Hitherto though, knowledge on PADs in PDAC is limited. In the current study, two PDAC cell lines (Panc-1 and MiaPaCa-2) were treated with pan-PAD inhibitor Cl-amidine as well as PAD2, PAD3, and PAD4 isozyme-specific inhibitors. Effects were assessed on changes in EV signatures, including EV microRNA cargo (miR-21, miR-126, and miR-221), on changes in cellular protein expression relevant for pancreatic cancer progression and invasion (moesin), for mitochondrial housekeeping (prohibitin, PHB), and gene regulation (deiminated histone H3, citH3). The two pancreatic cancer cell lines were found to predominantly express PAD2 and PAD3, which were furthermore expressed at higher levels in Panc-1, compared with MiaPaCa-2 cells. PAD2 isozyme-specific inhibitor had the strongest effects on reducing Panc-1 cell invasion capability, which was accompanied by an increase in moesin expression, which in pancreatic cancer is found to be reduced and associated with pancreatic cancer aggressiveness. Some reduction, but not significant, was also found on PHB levels while effects on histone H3 deimination were variable. EV signatures were modulated in response to PAD inhibitor treatment, with the strongest effects observed for PAD2 inhibitor, followed by PAD3 inhibitor, showing significant reduction in pro-oncogenic EV microRNA cargo (miR-21, miR-221) and increase in anti-oncogenic microRNA cargo (miR-126). While PAD2 inhibitor, followed by PAD3 inhibitor, had most effects on reducing cancer cell invasion, elevating moesin expression, and modulating EV signatures, PAD4 inhibitor had negligible effects and pan-PAD inhibitor Cl-amidine was also less effective. Compared with MiaPaCa-2 cells, stronger modulatory effects for the PAD inhibitors were observed in Panc-1 cells, which importantly also showed strong response to PAD3 inhibitor, correlating with previous observations that Panc-1 cells display neuronal/stem-like properties. Our findings report novel PAD isozyme regulatory roles in PDAC, highlighting roles for PAD isozyme-specific treatment, depending on cancer type and cancer subtypes, including in PDAC.

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“…28 Amounts of evidence showed that miRNAs played important roles in cancers, including tumorigenesis, cell signaling transduction, cell proliferation, apoptosis, tumor invasion and metastasis. [29][30][31] Recently, a novel regulatory mechanism, called ceRNA hypothesis, has been proposed, wherein specific RNAs can impair miRNAs activity through competing with shared miRNAs response elements (MREs), thereby upregulating miRNAs target gene expression. 32 For example, circMLLT10 promotes gastric cancer cell growth and metastasis via sponging miR-509-3-5p to promote GINS4 expression.…”

Section: Introductionmentioning

confidence: 99%