Karyopherinβ1 regulates proliferation of human glioma cells via Wnt/β-catenin pathway

Lü, Ting; Bao, Zhen; Wang, Yunfeng; Yang, Lixiang; Lu, Bing; Ke, Ya; Wang, Shaozhen; He, Wei; Zhang, Zhe; Cui, Gang

doi:10.1016/j.bbrc.2016.08.093

Cited by 37 publications

(33 citation statements)

References 33 publications

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“…Among these genes, CDH1 and Notch-1 (Figure 4A) are regarded as the regulators of Wnt/β-catenin and PI3K/Akt signaling pathways, respectively [21,22]. As the two pathways are always activated in glioma cells and GSCs [23,24,25,26], we hypothesize that CDH1 and Nocth-1 could be the direct targets of miR-92a. To test our hypothesis, qRT-PCR and Western blotting assay were applied to measure the relative expression levels of CDH1 and Notch-1 in two cell types.…”

Section: Resultsmentioning

confidence: 99%

miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

Song

Zhang

Liu

et al. 2016

IJMS

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MicroRNAs (miRNAs) are implicated in the regulation of tumor progression and stemness of cancer stem-like cells. Recently, miR-92a-3p was reported to be up-regulated in human glioma samples. Nevertheless, the precise role of miR-92a-3p in glioma cells and glioma stem-like cells (GSCs) has not been fully elucidated. It is necessary to clarify the function of miR-92a-3p in glioma and GSCs to develop novel therapeutic approaches for glioma patients. In the present study, we applied methyl-thiazolyl-tetrazolium (MTT) assay and Transwell assay to measure the proliferation rate and metastatic potential of glioma cells. Meanwhile, the self-renewal ability of GSCs was detected by tumor sphere formation assay. The results revealed that down-regulation of miR-92a-3p suppressed the glioma cell malignancy in vitro. Moreover, knockdown of miR-92a-3p led to a reduction of tumorgenesis in vivo. Interestingly, we also observed that up-regulation of miR-92a-3p could inhibit the stemness of GSCs. Subsequent mechanistic investigation indicated that cadherin 1 (CDH1)/β-catenin signaling and Notch-1/Akt signaling were the downstream pathways of miR-92a-3p in glioma cells and GSCs, respectively. These results suggest that miR-92a-3p plays different roles in glioma cells and GSCs through regulating different signaling pathways.

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Section: Resultsmentioning

confidence: 99%

miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

Song

Zhang

Liu

et al. 2016

IJMS

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“…Increased KPNB1 protein levels have been reported in several cancers, including cervical cancer (42), hepatocellular carcinoma (43), and glioma (44), suggesting KPNB1's oncogenic potential in these tumor types. In this study, we validated an oncogenic function of KPNB1 in EOC through apoptosis inhibition and cell cycle progression.…”

Section: Discussionmentioning

confidence: 99%

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer

Kodama

Newberg

et al. 2017

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

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Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has not been changed significantly during several decades. To seek new therapeutic targets for EOC, we performed an in vivo dropout screen in human tumor xenografts using a pooled shRNA library targeting thousands of druggable genes. Then, in follow-up studies, we performed a second screen using a genome-wide CRISPR/Cas9 library. These screens identified 10 high-confidence drug targets that included well-known oncogenes such as ERBB2 and RAF1, and novel oncogenes, notably KPNB1, which we investigated further. Genetic and pharmacological inhibition showed that KPNB1 exerts its antitumor effects through multiphase cell cycle arrest and apoptosis induction. Mechanistically, proteomic studies revealed that KPNB1 acts as a master regulator of cell cycle-related proteins, including p21, p27, and APC/ C. Clinically, EOC patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1. Interestingly, ivermectin, a Food and Drug Administration-approved antiparasitic drug, showed KPNB1-dependent antitumor effects on EOC, serving as an alternative therapeutic toward EOC patients through drug repositioning. Last, we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC both in vitro and in vivo than either drug alone. Our studies have thus identified a combinatorial therapy for EOC, in addition to a plethora of potential drug targets.ovarian cancer | KPNB1 | loss-of-function screen | CRISPR/Cas | RNAi

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“…Despite current treatments of neurosurgery and chemoradiotherapy, median survival remains around 14.6 months, and 5-year survival is <5% 5,7. Lu et al showed that the relative expression of KPNβ 1 correlated with the World Health Organization (WHO) grades of human glioma, with higher expression of KPNβ 1 correlating with more severe WHO glioma classification 5. Additionally, higher expression of KPNβ 1 correlated with lower 5-year survival ratio on Kaplan–Meier survival curves 5.…”

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confidence: 99%

“…KPNβ 1 has recently been shown to regulate proliferation of human glioma cells via the Wnt–β-catenin pathway 5. Glioblastoma multiforme is the most frequent brain cancer in adults and is highly infiltrative 6.…”

mentioning

confidence: 99%

“…Glioblastoma multiforme is the most frequent brain cancer in adults and is highly infiltrative 6. Despite current treatments of neurosurgery and chemoradiotherapy, median survival remains around 14.6 months, and 5-year survival is <5% 5,7. Lu et al showed that the relative expression of KPNβ 1 correlated with the World Health Organization (WHO) grades of human glioma, with higher expression of KPNβ 1 correlating with more severe WHO glioma classification 5.…”

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confidence: 99%

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The role of KPNβ<sub>1</sub> in neuro-oncology

Lilley¹,

Farassati²

2017

OTT

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Karyopherinβ1 regulates proliferation of human glioma cells via Wnt/β-catenin pathway

Cited by 37 publications

References 33 publications

miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer

The role of KPNβ<sub>1</sub> in neuro-oncology

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Karyopherinβ1 regulates proliferation of human glioma cells via Wnt/β-catenin pathway

Cited by 37 publications

References 33 publications

miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer

The role of KPN&beta;<sub>1</sub> in neuro-oncology

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The role of KPNβ<sub>1</sub> in neuro-oncology