Identification of miRNAs that are associated with tumor metastasis in Neuroblastoma

Guo, Jingheng; Dong, Qian; Fang, Zhixiang; Chen, Xi; Lu, Hongting; Wang, Kehui; Yuan, Yin; Cai, Xing Fu; Zhao, Nan; Chen, Jiangning; Zen, Ke; Zhang, Junfeng; Zhang, Chenyu

doi:10.4161/cbt.9.6.10894

Cited by 47 publications

(56 citation statements)

References 22 publications

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“…Previous studies indicated that there are many miRNAs deregulated in metastatic NB tissues using miRNA profiling [11,12], but there were few reports about the regulation mechanism of miRNAs in metastatic NB. MiR-335 inhibits NB cell invasion by regulating many genes that are involved in the non-canonical TGF-b signaling pathway [13].…”

Section: Introductionmentioning

confidence: 99%

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MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7

Li¹,

Wang²,

Li³

et al. 2014

ABBS

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MicroRNAs (miRNAs) function as key regulators of gene expression in various cancers. In this study, the aim is to explore the roles and regulation mechanism of miR-181c in neuroblastoma (NB) cells. We found that miR-181c was downregulated in metastatic NB tissues, compared with primary NB tissues. Then functional studies indicated that miR-181c overexpression inhibited NB cell proliferation, migration, and invasion, while miR-181c inhibition increased cell proliferation, migration, and invasion. EGFP reporter assay, real-time polymerase chain reaction and western blot analysis validated that Smad7 was a direct target of miR181c. MiR-181c reduced Smad7 expression at both mRNA and protein levels. Finally, functional assays showed that the effect of Smad7 knockdown on cells was similar to that of miR-181c overexpression. Importantly, Smad7 overexpression could restore the antitumor effects that were induced by miR-181c. In conclusion, our results demonstrated that miR181c inhibits NB cell growth and metastasis-related traits through the suppression of Smad7, functioning as a tumor suppressor. Moreover, our results suggested that miR-181c may serve as an important therapeutic target for NB patients.

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Section: Introductionmentioning

confidence: 99%

“…MiR-15a promotes NB cell migration and growth through miR-15a/RECK/MMP-9 axis [16]. Among the miRNA expression profiling in NB tissues, miR-181c is downregulated [11]. However, the roles and regulation mechanism of miR-181c in metastatic NB is yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7

Li¹,

Wang²,

Li³

et al. 2014

ABBS

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show abstract

“…8 Specifically, miR-335 has been shown to act as a suppressor of tumor metastasis by regulating TGF-β non-canonical pathways leading to inactivation of the motor protein myosin light chain which results in decreased migratory and invasive potential of neuroblastoma cells. 9 miR-335 has been shown to have similar anti-metastatic properties in breast cancer by targeting sex determining region Y-box 4 (SOX4) and tenascin C (TNC).…”

Section: Introductionmentioning

confidence: 99%

miR-335 and miR-363 regulation of neuroblastoma tumorigenesis and metastasis

Qiao

Lee

Paul

et al. 2013

Surgery

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Background microRNA (miRNA) functions broadly as post-transcriptional regulators of gene expression, and disproportionate miRNAs can result in dysregulation of oncogenes in cancer cells. We have previously shown that gastrin-releasing peptide receptor (GRP-R) signaling regulates tumorigenicity of neuroblastoma cells. Here, we sought to characterize miRNA profile in GRP-R silenced neuroblastoma cells, and to determine the role of miRNAs on tumorigenicity and metastatic potential. Methods Human neuroblastoma cell lines, BE(2)-C and SK-N-SH, were used for our study. Stably-transfected GRP-R silenced cells were assessed for miRNA profiles. Cells were transfected with miR-335, miR-363, or miR-CON, a non-targeting control, and in vitro assays were performed. In vivo functions of miR-335 and miR-363 were also assessed in spleen-liver metastasis murine model. Results GRP-R silencing significantly increased expression of miR-335 and miR-363 in BE(2)-C cells. Overexpression of miR-335 and miR-363 decreased tumorigenicity as measured by clonogenicity, anchorage-independent growth, and metastasis determined by cell invasion assay and liver metastasis in vivo. Conclusions We report, for the first time, that GRP-R-mediated tumorigenicity and increased metastatic potential in neuroblastoma are regulated, in part, by miR-335 and miR-363. A better understanding of the anti-tumor functions of miRNAs could provide valuable insights to discerning molecular mechanisms responsible for neuroblastoma metastasis.

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“…Endogenous miRNAs play important roles in a variety of processes, such as development, cell proliferation, differentiation, and apoptosis (16). Dysregulated miRNA expression also frequently occurs in various types of cancers, including neuroblastoma (17)(18)(19). Notably, a large number of miRNAs have been reported to be differentially expressed between MYCN-amplified and MYCNnonamplified neuroblastoma tumors, adding new layers of complexity to the mechanisms underlying MYCN-mediated neuroblastoma tumorigenesis (20,21).…”

Section: Introductionmentioning

confidence: 99%

microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma

Tan

Mou

et al. 2017

Clinical Cancer Research

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Purpose: MYCN is one of the most well-characterized genetic markers of neuroblastoma. However, the mechanisms as to how MYCN mediate neuroblastoma tumorigenesis are not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated neuroblastoma tumorigenesis, supporting their potential as therapeutic targets for neuroblastoma. Although miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated neuroblastoma progression remains largely elusive.Experimental Design: The expression of miR-221 in the formalin-fixed, paraffin-embedded tissues from 31 confirmed patients with neuroblastoma was detected by locked nucleic acid-in situ hybridization and qRT-PCR. The correlation between miR-221 expression and clinical features in patients with neuroblastoma was assessed. The mechanisms as to how miR-221 regulate MYCN in neuroblastoma were addressed. The effect of miR-221 on cellular proliferation in neuroblastoma was determined both in vitro and in vivo.Results: miR-221 was significantly upregulated in neuroblastoma tumor cells and tissues that overexpress MYCN, and high expression of miR-221 was positively associated with poor survival in patients with neuroblastoma. Nemo-like kinase (NLK) as a direct target of miR-221 in neuroblastoma was verified. In addition, overexpression of miR-221 decreased LEF1 phosphorylation but increased the expression of MYCN via targeting of NLK and further regulated cell cycle, particularly in S-phase, promoting the growth of neuroblastoma cells.Conclusions: This study provides a novel insight for miR-221 in the control of neuroblastoma cell proliferation and tumorigenesis, suggesting potentials of miR-221 as a prognosis marker and therapeutic target for patients with MYCN overexpressing neuroblastoma.

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Identification of miRNAs that are associated with tumor metastasis in Neuroblastoma

Cited by 47 publications

References 22 publications

MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7

MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7

miR-335 and miR-363 regulation of neuroblastoma tumorigenesis and metastasis

microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma

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