Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR

Huang, Tsui-Chin; Chang, Ho‐Myung; Chen, Cheng-Yu; Wu, Pei Yi; Lee, Hsinyu; Liao, Yung Feng; Hsu, Wen Ming; Huang, Hsuan Cheng; Juan, Hsueh‐Fen

doi:10.1016/j.febslet.2011.10.025

Cited by 67 publications

(44 citation statements)

References 25 publications

(30 reference statements)

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“…Our findings are in keeping with previous data indicating that metabolic pathways are critical in ccRCC pathogenesis (17 ), and we showed that AHR signaling is altered in ccRCC. We identified and validated AHR as an overexpressed gene that is regulated by the underexpressed miR-124 in ccRCC, an interaction that already has been experimentally validated in other tumors (18 ). AHR can mediate either tumor-promoting or -inhibiting effects.…”

Section: Discussionmentioning

confidence: 84%

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

et al. 2014

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BACKGROUND The outcome of clear cell renal cell carcinoma (ccRCC) is still unpredictable. Even with new targeted therapies, the average progression-free survival is dismal. Markers for early detection and progression could improve disease outcome. METHODS To identify efficient and hitherto unrecognized pathogenic factors of the disease, we performed a uniquely comprehensive pathway analysis and built a gene interaction network based on large publicly available data sets assembled from 28 publications, comprising a 3-prong approach with high-throughput mRNA, microRNA, and protein expression profiles of 593 ccRCC and 389 normal kidney samples. We validated our results on 2 different data sets of 882 ccRCC and 152 normal tissues. Functional analyses were done by proliferation, migration, and invasion assays following siRNA (small interfering RNA) knockdown. RESULTS After integration of multilevel data, we identified aryl-hydrocarbon receptor (AHR), grainyhead-like-2 (GRHL2), and KIAA0101 as new pathogenic factors. GRHL2 expression was associated with higher chances for disease relapse and retained prognostic utility after controlling for grade and stage [hazard ratio (HR), 3.47, P = 0.012]. Patients with KIAA0101-positive expression suffered worse disease-free survival (HR, 3.64, P < 0.001), and in multivariate analysis KIAA0101 retained its independent prognostic significance. Survival analysis showed that GRHL2- and KIAA0101-positive patients had significantly lower disease-free survival (P = 0.002 and P < 0.001). We also found that KIAA0101 silencing decreased kidney cancer cell migration and invasion in vitro. CONCLUSIONS Using an integrative system biology approach, we identified 3 novel factors as potential biomarkers (AHR, GRHL2 and KIAA0101) involved in ccRCC pathogenesis and not linked to kidney cancer before.

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Section: Discussionmentioning

confidence: 84%

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

et al. 2014

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“…However, miR-124 may be present in neuroblastoma but not in all types of tumours [34]. This reflects the heterogeneity and complexity of tumors; further research should be carried out to discover the mechanisms by which miR-124 differentially affects the proliferation of breast cancer and neuroblastoma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 Suppresses Breast Cancer Cell Growth and Motility by Targeting CD151

Han¹,

Yang²,

Cheng³

et al. 2013

Cell Physiol Biochem

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Background: CD151 is highly expressed in breast cancer cells and has been shown to accelerate breast cancer by enhancing cell growth and motility, but its regulation is poorly understood. To explore post-translation regulation of CD151, for example microRNAs, will be of great importance to claim the mechanism. Methods: A luciferase reporter assay was used to determine whether CD151 was a target of miR-124. The levels of CD151 mRNA were detected by real-time PCR and CD151 protein expression was measured by western blot and flow cytometry. The effects of miR-124 expression on growth, apoptosis, cell cycle and motility of breast cancer cells were determined. Results: We discovered that miR-124 directly targets the 3' untranslated region (3'-UTR) of CD151 mRNAs and suppresses its mRNA expression and protein translation. Both siRNA of CD151 and miR-124 mimics could significantly inhibit proliferation of breast cancer cell lines via cell cycle arrest but does not induce apoptosis. Meanwhile, miR-124 mimics significantly inhibited the motility of breast cancer cells. Conclusion: miR-124 plays a critical role in inhibiting the invasive and metastatic potential of breast cancer cells, probably by directly targeting the CD151 genes. Our findings highlight an important role of miR-124 in the regulation of invasion and metastasis by breast cancer cells and suggest a potential application for miR-124 in breast cancer treatment.

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“…By mediating inhibition of CDK6, which can regulate both cell cycle progression and differentiation [31], the up-regulation of miR-124 induced neuronal differentiation of brain tumor stem cells and inhibited proliferation of glioblastoma multiforme cell lines [29]. On the other hand, a recent research that knockdown of miR-124 promotes neuroblastoma cell differentiation, cell cycle arrest and apoptosis, indicated that miR-124 might exert diverse functions in differentiation of different cancers [32]. Thus, in agreement with these studies, our results may suggest that miR-124 play a role in the differentiation of colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer

Wang

et al. 2012

Int J Colorectal Dis

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Purpose Recently, has been demonstrated as a potential tumor suppressor in several types of cancers. However, the role of miR-124 in colorectal cancer remains unclear. This study was aimed at investigating the clinicopathological significance of miR-124 expression in colorectal cancer. Conclusions MiR-124 may play a certain role in the development of colorectal cancer. The downregulation expression of miR-124 is an independent prognostic factor in patients with colorectal cancer. Methods

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Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR

Cited by 67 publications

References 25 publications

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

MicroRNA-124 Suppresses Breast Cancer Cell Growth and Motility by Targeting CD151

Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer

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