MicroRNA‐23b mediates urokinase and c‐met downmodulation and a decreased migration of human hepatocellular carcinoma cells

Salvi, Alessandro; Sabelli, Cristiano; Moncini, Silvia; Venturin, Marco; Arici, Bruna; Riva, Paola; Portolani, Nazario; Giulini, Stefano Maria; Petro, Giuseppina De; Barlati, Sergio

doi:10.1111/j.1742-4658.2009.07014.x

Cited by 138 publications

(124 citation statements)

References 42 publications

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“…2). We showed that AM23b reversed the EC growth arrest under PS; this is in concert with the finding that miR-23b overexpression decreases hepatocelluar carcinoma cell proliferation (39). Although both AM23b and AM27b can regulate E2F1 expression, only AM23b significantly reduced the PS-induced Rb hypophosphorylation and cell cycle arrest.…”

Section: Discussionsupporting

confidence: 85%

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Wang

Garmire

Young

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

158

132

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MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological responses of ECs are regulated by not only mRNA and protein signaling networks, but also expression of the corresponding miRs. EC growth arrest induced by pulsatile shear (PS) flow is an important feature for flow regulation of ECs. miR profiling showed that 21 miRs are differentially expressed (8 up-and 13 downregulated) in response to 24-h PS as compared to static condition (ST). The mRNA expression profile indicates EC growth arrest under 24-h PS. Analysis of differentially expressed miRs yielded 68 predicted mRNA targets that overlapped with results of microarray mRNA profiling. Functional analysis of miR profile indicates that the cell cycle network is highly regulated. The upregulation of miR-23b and miR-27b was found to correlate with the PS-induced EC growth arrest. Inhibition of miR-23b using antagomir-23b oligonucleotide (AM23b) reversed the PSinduced E2F1 reduction and retinoblastoma (Rb) hypophosphorylation and attenuated the PS-induced G1/G0 arrest. Antagomir AM27b regulated E2F1 expression, but did not affect Rb and growth arrest. Our findings indicate that PS suppresses EC proliferation through the regulation of miR-23b and provide insights into the role of miRs in mechanotransduction.cell cycle | shear | bioinformatics | gene regulation | mechanotransduction H emodynamic forces, e.g., stretch and shear stress, act constantly on the vascular endothelial cells (ECs) to modulate EC signaling, gene expression, and physiological functions (1). Atherosclerotic lesions in the arterial tree are found mainly at branch points, where blood flow is disturbed with a limited forwarding direction, but are generally spared at the straight parts of the arterial tree, where the flow is laminar with a large forwarding direction (2). Exposure of ECs to 24 h of steady laminar shear flow at 12 dyn/cm 2 (approximating the hemodynamic force in straight parts of arteries) leads to antiproliferative (3) and antiinflammatory (4) responses. In contrast, ECs exposed to disturbed flow, mimicking the hemodynamic force at branch points, exhibit opposite responses (5, 6). The laminar shear-induced EC growth arrest involves the expression of CDK inhibitors (e.g., p21 cip , p27 kip ), tumor suppressor p53, and retinoblastoma (Rb) hypophosphorylation (3, 7). Whereas there is considerable knowledge on mechanotransduction at protein and mRNA levels, there is little information on the role of microRNAs (miRs) in this process.miRs are small noncoding RNAs (∼21-25 nucleotides) that regulate gene expression by binding to target mRNAs to cause their degradation or translational repression (8). It is estimated that miRs regulate ∼30% of human protein-coding genes. More than 800 miRs have been identified in the human genome and registered in the Sanger miRBase. These small RNAs provide a powerful mechanism for posttranscriptional cont...

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Section: Discussionsupporting

confidence: 85%

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Wang

Garmire

Young

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

158

132

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“…Although a few studies recently demonstrated that miR-23b is involved in invasion and metastasis, the molecular mechanism remains to be elucidated 30,31 . Th e data reported here demonstrated that miR-23b, which is downregulated in human colon cancer samples, could potently repress cancer cell migration, invasion, growth and angiogenesis both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

et al. 2011

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miRNA globally deregulates human carcinoma. A critical open question is how many miRNAs functionally participate in cancer development, particularly in metastasis. We systematically evaluate the capability of all known human miRNAs to regulate certain metastasis-relevant cell behaviours. To perform the high-throughput screen of miRNAs, which regulate cell migration, we developed a novel self-assembled cell microarray. Here we show that over 20 % of miRNAs have migratory regulation activity in diverse cell types, indicating a general involvement of miRNAs in migratory regulation. MiR-23b, which is downregulated in human colon cancer samples, potently mediates the multiple steps of metastasis, including tumour growth, invasion and angiogenesis in vivo . It regulates a cohort of prometastatic targets, including FZD7 or MAP3k1 . These fi ndings provide new insight into the physiological and potential therapeutic importance of miRNAs as a new class of functional modulators.

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“…The activation of c-Met through aberrant hepatocyte growth factor paracrine stimulation contributes to tumor invasion and metastasis, with overexpression of c-Met associated with bladder cancer progression and poor prognosis (Cheng et al, 2002;2005). The microRNAs miR-23b, miR-34a and miR-198 have been reported to inhibit migration and invasion through down-regulation of c-Met expression in human hepatocellular carcinoma cells (Li et al, 2009;Salvi et al, 2009;Tan et al, 2011). Another report indicates that the anti-metastatic miR-340 inhibits breast cancer metastasis by targeting c-Met (Wu et al, 2011).…”

Section: A B C Dmentioning

confidence: 99%

MicroRNA-409-3p Inhibits Migration and Invasion of Bladder Cancer Cells via Targeting c-Met

Chen

Lin

et al. 2013

Molecules and Cells

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There is increasing evidence suggesting that dysregulation of certain microRNAs (miRNAs) may contribute to tumor progression and metastasis. Previous studies have shown that miR-409-3p is dysregulated in some malignancies, but its role in bladder cancer is still unknown. Here, we find that miR-409-3p is down-regulated in human bladder cancer tissues and cell lines. Enforced expression of miR-409-3p in bladder cancer cells significantly reduced their migration and invasion without affecting cell viability. Bioinformatics analysis identified the pro-metastatic gene c-Met as a potential miR-409-3p target. Further studies indicated that miR-409-3p suppressed the expression of cMet by binding to its 3′-untranslated region. Silencing of cMet by small interfering RNAs phenocopied the effects of miR-409-3p overexpression, whereas restoration of c-Met in bladder cancer cells bladder cancer cells overexpressing miR-409-3p, partially reversed the suppressive effects of miR-409-3p. We further showed that MMP2 and MMP9 may be downstream effector proteins of miR-409-3p. These findings indicate that miR-409-3p could be a potential tumor suppressor in bladder cancer.

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MicroRNA‐23b mediates urokinase and c‐met downmodulation and a decreased migration of human hepatocellular carcinoma cells

Cited by 138 publications

References 42 publications

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

MicroRNA-409-3p Inhibits Migration and Invasion of Bladder Cancer Cells via Targeting c-Met

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