Mechanism of growth inhibition by MicroRNA 145: The role of the IGF‐I receptor signaling pathway

Rocca, Gaspare La; Badin, Margherita; Shu, Bin; Xu, Shi-Qiong; DeAngelis, Tiziana; Sepp-Lorenzinoi, Laura; Baserga, Renato

doi:10.1002/jcp.21796

Cited by 112 publications

(95 citation statements)

References 41 publications

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“…7 The cells seemed to stop growing, an observation that was confirmed in 3T3 cells transfected with mir145. 10 This is compatible with downregulation of IRS-1. There are normal cells and many cell lines that do not express IRS-1, or express very low levels, and these cells grow in 10% serum, although they are prone to differentiation (reviewed in ref.…”

Section: Introductionmentioning

confidence: 62%

“…The finding by LaRocca et al 10 that an IRS-1 without its 3'UTR rescues HCT116 ex5 cells from miR145-induced growth arrest was surprising. Most, if not all miRs have multiple targets, according to the databases.…”

Section: Discussionmentioning

confidence: 97%

“…Only IRS-1 without its 3'UTR rescued HCT116 cells from miR145 inhibition of growth. 10 These experiments suggested that the tumor suppressor activity of miR145 was largely due to targeting of IRS-1, although miR145, like most miRs, targets (at least according to the database) many mRNAs. miR145 inhibition of HCT116 cells growth was characterized as growth arrest or growth inhibition, although some dead cells could be identified in later stages.…”

Section: Introductionmentioning

confidence: 99%

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Growth inhibition by microRNAs that target the insulin receptor substrate-1

Rocca

Shi²,

Badin³

et al. 2009

Cell Cycle

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We have examined several microRNAs (miRs) indicated by the databases as targeting the signaling pathway of the type-1 insulin-like growth factor receptor (IGF-IR). Most of the miRs tested had multiple targets, as expected, leading to cell death. However, miR145 seemed to affect its tumor suppressor activity largely by downregulating the docking protein of the IGF-IR, the insulin receptor substrate-1 (IRS-1). These results suggest that, despite the many targets provided by the databases, in some cases a single target can be predominant in determining the end results.

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Section: Introductionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Growth inhibition by microRNAs that target the insulin receptor substrate-1

Rocca

Shi²,

Badin³

et al. 2009

Cell Cycle

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“…Indeed, miR-145 is a widely accepted tumor suppressor in human cancers and targets various oncogenes in cancer cells. 17,18,23,24 The miRNA signature described here includes approved miRNAs that are downregulated in human cancers, including PCa, and indicates the effectiveness of this signature for cancer research.…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer

et al. 2012

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microRNAs (miRNAs) have key roles in human tumorigenesis, tumor progression and metastasis. miRNAs are aberrantly expressed in many human cancers and can function as tumor suppressors or oncogenes that target many cancer-related genes. This study seeks to identify novel miRNA-regulated molecular pathways in prostate cancer (PCa). The miRNA expression signature in clinical specimens of PCa showed that 56 miRNAs were significantly downregulated in PCa compared with nonPCa tissues. We focused on the top four downregulated miRNAs (miR-187, miR-205, miR-222 and miR-31) to investigate their functional significance in PCa cells. Expression levels of these four miRNAs were validated in PCa specimens (15 PCa tissues and 17 non-PCa tissues) to confirm that they were significantly reduced in these PCa tissues. Gain-of-function analysis demonstrated that miR-222 and miR-31 inhibited cell proliferation, invasion and migration in PCa cell lines (PC3 and DU145), suggesting that miR-222 and miR-31 may act as tumor suppressors in PCa. Genome-wide gene expression analysis using miR-222 or miR-31 transfectants to identify the pathways they affect showed that many cancer-related genes are regulated by these miRNAs in PC3 cells. Identification and categorization of the molecular pathways regulated by tumor suppressive miRNAs could provide new information about the molecular mechanisms of PCa tumorigenesis.

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“…Through functional studies, miR-145 has shown the dual tumor-suppressive and oncogenic phenotypes in different cell lines and animal models. miR-145 suppresses tumor cell growth by targeting insulin receptor substrate-1 (45), type I insulin-like growth factor receptor (46), and c-Myc (47). Meanwhile, miR-145 impacts the migration, invasion, and metastasis of cancer cells by targeting mucin 1 (48) and N-cadherin (49), and also affects p53-mediated cell-cycle arrest by targeting p21 (47).…”

Section: ) Ets1 Is Also Implicated In Vascularizationmentioning

confidence: 99%

miRNA-145 Targets v-ets Erythroblastosis Virus E26 Oncogene Homolog 1 to Suppress the Invasion, Metastasis, and Angiogenesis of Gastric Cancer Cells

Zheng

et al. 2013

Molecular Cancer Research

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Recent evidence shows that v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) is implicated in tumor development and progression. However, the clinical potentials and underlying mechanisms of Ets1 in gastric cancer progression and metastasis remain largely unknown. In this study, Ets1 immunostaining was identified in 56 of 84 (66.7%) gastric cancer tissues, which was correlated with tumor invasion and metastasis. In gastric cancer specimens and cell lines, miRNA-145 (miR-145) was downregulated and inversely correlated with Ets1 expression. Bioinformatics analysis and luciferase reporter assay revealed that miR-145 directly targeted the 3 0 -untranslated region (3 0 -UTR) of Ets1 mRNA. Overexpression or knockdown of miR-145 responsively altered both the mRNA and protein levels of Ets1 and its downstream genes, matrix metalloproteinase (MMP-1)-1 and -9, in gastric cancer cell lines SGC-7901 and MKN-45. Ectopic expression of miR-145 suppressed the invasion, metastasis, and angiogenesis of SGC-7901 and MKN-45 cells in vitro and in vivo. In addition, the effects of miR-145 on Ets1 expression, migration, invasion, and angiogenesis were rescued by restoration of Ets1 expression in these cells. Furthermore, anti-miR-145 inhibitor promoted the migration, invasion, and angiogenesis, whereas siRNAmediated Ets1 knockdown phenocopied the effects of miR-145 overexpression in gastric cancer cells. These results show that miR-145 suppresses Ets1 expression via the binding site in the 3 0 -UTR, thus inhibiting the invasion, metastasis, and angiogenesis of gastric cancer cells. Mol Cancer Res; 11(2); 182-93. Ó2012 AACR.

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Mechanism of growth inhibition by MicroRNA 145: The role of the IGF‐I receptor signaling pathway

Cited by 112 publications

References 41 publications

Growth inhibition by microRNAs that target the insulin receptor substrate-1

Growth inhibition by microRNAs that target the insulin receptor substrate-1

Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer

miRNA-145 Targets v-ets Erythroblastosis Virus E26 Oncogene Homolog 1 to Suppress the Invasion, Metastasis, and Angiogenesis of Gastric Cancer Cells

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