IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells

Dong, Cheng; Zhang, Junwen; Fang, Sheng; Liu, Fusheng

doi:10.1186/s13008-020-00061-6

Cited by 36 publications

(33 citation statements)

References 41 publications

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“…Among them, ARHGAP11A, DRP2, HNRNPA3, KLF10, PAIP1, and RCN1 have not yet been studied in gliomas. Three mRNAs were identified as oncogenes in gliomas, which was consistent with our multivariate Cox regression analysis result: IGFBP5 can increase cell invasion and inhibit cell proliferation via the EMT and Akt signaling pathways in GBM ( Dong et al, 2020 ); IP6K2 was reported to promote cell proliferation and inhibit cell apoptosis under the regulation of the LINC00467/miR-339-3p axis ( Liang & Tang, 2020 ); and KPNA4 is capable of facilitating epithelial-mesenchymal transition in glioma, which can be suppressed by miR-181b, a tumor-suppressive miRNA ( Wang et al, 2015 ). Surprisingly, the roles of the other two mRNAs in glioma were shown to be different from our analysis result: NRP2 promoted glioma cell growth, invasion, and angiogenesis ( Zheng et al, 2013 ); and SEMA5A, whose expression is markedly reduced in higher grades of glioma, can impede motility and promote differentiation of human gliomas ( Li & Lee, 2010 ).…”

Section: Discussionsupporting

confidence: 85%

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

Chen

Tong

et al. 2021

PeerJ

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Background Glioma is the most common brain neoplasm with a poor prognosis. Circular RNA (circRNA) and their associated competing endogenous RNA (ceRNA) network play critical roles in the pathogenesis of glioma. However, the alteration of the circRNA-miRNA-mRNA regulatory network and its correlation with glioma therapy haven’t been systematically analyzed. Methods With GEO, GEPIA2, circBank, CSCD, CircInteractome, mirWalk 2.0, and mirDIP 4.1, we constructed a circRNA–miRNA–mRNA network in glioma. LASSO regression and multivariate Cox regression analysis established a hub mRNA signature to assess the prognosis. GSVA was used to estimate the immune infiltration level. Potential anti-glioma drugs were forecasted using the cMap database and evaluated with GSEA using GEO data. Results A ceRNA network of seven circRNAs (hsa_circ_0030788/0034182/0000227/ 0018086/0000229/0036592/0002765), 15 miRNAs(hsa-miR-1200/1205/1248/ 1303/3925-5p/5693/581/586/599/607/640/647/6867-5p/767-3p/935), and 46 mRNAs (including 11 hub genes of ARHGAP11A, DRP2, HNRNPA3, IGFBP5, IP6K2, KLF10, KPNA4, NRP2, PAIP1, RCN1, and SEMA5A) was constructed. Functional enrichment showed they influenced majority of the hallmarks of tumors. Eleven hub genes were proven to be decent prognostic signatures for glioma in both TCGA and CGGA datasets. Forty-six LASSO regression significant genes were closely related to immune infiltration. Finally, five compounds (fulvestrant, tanespimycin, mifepristone, tretinoin, and harman) were predicted as potential treatments for glioma. Among them, mifepristone and tretinoin were proven to inhibit the cell cycle and DNA repair in glioma. Conclusion This study highlights the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identifies novel therapeutic options for glioma.

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Section: Discussionsupporting

confidence: 85%

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

Chen

Tong

et al. 2021

PeerJ

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“…Nevertheless, in gliomas, elevated levels of tissue IGFBP5 were associated with higher tumor grades and poor prognosis ( 36–38 ). Silencing IGFBP5 expression impedes invasion but promotes the proliferation of GBM cells in vitro , thus having opposing effects on two cellular hallmarks of neoplastic state ( 39 ).…”

Section: Introductionmentioning

confidence: 99%

MN1overexpression with varying tumor grade is a promising predictor of survival of glioma patients

Saini

Jha

Tangri

et al. 2020

Human Molecular Genetics

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Gliomas have substantial mortality to incidence rate ratio and a dismal clinical course. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. Meningioma 1 (MN1) gene is a transcriptional co-regulator implicated in other malignancies, albeit its significance in glioma pathology remains to be explored. IGFBP5 is regulated transcriptionally by MN1 and IGF1, and is associated with higher glioma grade and shorter survival time, prompting us to ascertain their correlation in these tumors. We quantified MN1, IGFBP5 and IGF1 expression in 40 glioma samples and examined their interrelatedness. MN1 mRNA-protein inter-correlation and gene’s copy number were evaluated in these tumors. Publicly available TCGA datasets were used to examine the association of MN1 expression levels with patient survival and for validating our findings. We observed MN1 overexpression correlated with low grade (LGGs) and not high grade gliomas (HGGs), and is not determined by copy number alteration of the gene. Notably, gliomas with upregulated MN1 have better overall and progression-free survival. IGFBP5 expression inversely associated with MN1 expression levels in gliomas but correlated positively with IGF1 expression in only LGGs. This suggests a potential grade-specific interplay between repressive and activating roles of MN1 and IGF1, respectively in the regulation of IGFBP5. Thus, MN1 overexpression, a promising predictor of overall and progression-free survival in gliomas, may serve as a prognostic biomarker in clinical practice to categorize patients with survival advantage.

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“…IGFBP-5 is highly expressed in GBM, indeed its depletion results in an inhibition of cell invasion and concomitant increase in cell proliferation. The double role of IGFBP-5 is mechanistically associated with Akt and EMT signaling ( 60 ).…”

Section: The Igf Signaling Pathway In Gbmmentioning

confidence: 99%

Prognostic and Therapeutic Roles of the Insulin Growth Factor System in Glioblastoma

et al. 2021

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Glioblastoma multiforme (GBM) is the most common primary brain malignancy and is often resistant to conventional treatments due to its extensive cellular heterogeneity. Thus, the overall survival of GBM patients remains extremely poor. Insulin-like growth factor (IGF) signaling entails a complex system that is a key regulator of cell transformation, growth and cell-cycle progression. Hence, its deregulation is frequently involved in the development of several cancers, including brain malignancies. In GBM, differential expression of several IGF system components and alterations of this signaling axis are linked to significantly worse prognosis and reduced responsiveness to temozolomide, the most commonly used pharmacological agent for the treatment of the disease. In the present review we summarize the biological role of the IGF system in the pathogenesis of GBM and comprehensively discuss its clinical significance and contribution to the development of resistance to standard chemotherapy and experimental treatments.

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IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells

Cited by 36 publications

References 41 publications

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

MN1overexpression with varying tumor grade is a promising predictor of survival of glioma patients

Prognostic and Therapeutic Roles of the Insulin Growth Factor System in Glioblastoma

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