PinX1 inhibits cell proliferation, migration and invasion in glioma cells

Mei, Peng-jin; Chen, Yansu; Du, Ying; Bai, Jing; Zheng, Junnian

doi:10.1007/s12032-015-0545-7

Cited by 10 publications

(8 citation statements)

References 29 publications

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“…In addition to the well-known effects of this pentacyclic acridine compound, here we report also its remarkable ability to upregulate the telomerase inhibitor PINX1, which has been recently reported as a suppressive gene in glioma through its ability to repress telomerase activity and cell invasion and migration [54]. Among NDIs, C2 was the most interesting agent, able to induce moderate telomere dysfunction, Bcl2 downregulation, ATR-CHK1 DNA damage response, cell cycle slowdown in S-phase coupled with PCC and apoptosis.…”

Section: Discussionsupporting

confidence: 56%

Naphthalene diimide‐derivatives G‐quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells

et al. 2018

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In the present paper, the biological effects of three different naphthalene diimides (NDIs) G-quadruplex (G4) ligands (H-NDI-Tyr, H-NDI-NMe2, and tetra-NDI-NMe2) were comparatively evaluated to those exerted by RHPS4, a well-characterized telomeric G4-ligand, in an in vitro model of glioblastoma. Data indicated that NDIs were very effective in blocking cell proliferation at nanomolar concentrations, although displaying a lower specificity for telomere targeting compared to RHPS4. In addition, differently from RHPS4, NDIs failed to enhance the effect of ionizing radiation, thus suggesting that additional targets other than telomeres could be involved in the strong NDI-mediated anti-proliferative effects. In order to test telomeric off-target action of NDIs, a panel of genes involved in tumor progression, DNA repair, telomere maintenance, and cell-cycle regulation were evaluated at transcriptional and translational level. Specifically, the compounds were able to cause a marked reduction of TERT and BCL2 amounts as well as to favor the accumulation of proteins involved in cell cycle control. A detailed cytofluorimetric analysis of cell cycle progression by means of bromodeoxyuridine (BrdU) incorporation and staining of phospho-histone H3 indicated that NDIs greatly reduce the progression through S-phase and lead to G1 accumulation of BrdU-positive cells. Taken together, these data indicated that, besides effects on telomeres and oncogenes such as Tert and Bcl2, nanomolar concentrations of NDIs determined a sustained block of cell proliferation by slowing down cell cycle progression during S-phase. In conclusion, our data indicate that NDIs G4-ligands are powerful antiproliferative agents, which act through mechanisms that ultimately lead to altered cell-cycle control.

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Section: Discussionsupporting

confidence: 56%

Naphthalene diimide‐derivatives G‐quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells

et al. 2018

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“…It has been reported that PinX1 suppress tumor growth and depletion of endogenous PinX1 enhanced tumorigenicity [32]. We observed that knockdown of PinX1 could also enhance cell proliferation and clonogenicity of NSCLC cell lines in vitro.…”

Section: Discussionmentioning

confidence: 51%

The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway

Tian

Jin

et al. 2017

Mol Cancer

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BackgroundThe telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. However, the clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear.MethodsPinX1 gene/expression pattern and its association with NSCLC patient survival were analyzed in cBioportal Web resource and two cohorts of NSCLC samples. A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on NSCLC cells proliferation and underlying mechanisms.ResultsMore frequency of gene PinX1 homozygous deletion and heterozygote deficiency was first retrieved from cBioportal Web resource. Low expression of PinX1 correlated with smoking condition, histological type, T stage, N stage, M stage and TNM stage, and was an independent predictor for overall survival in a learning cohort (n = 93) and a validation cohort (n = 51) of NSCLC patients. Furthermore, knockdown of PinX1 dramatically accelerated NSCLC cell proliferation and G1/S transition, whereas ectopic overexpression of PinX1 substantially inhibited cell viability and cell cycle transition in vitro and in vivo. p15/cyclin D1 pathway and BMP5 might contribute to PinX1-associated cell proliferation and cell cycle transition.ConclusionThe cost-effective expression of PinX1 could constitute a novel molecular predictor/marker for NSCLC management.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0637-4) contains supplementary material, which is available to authorized users.

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“…In the central nervous system, matrix metalloproteinases play a key role in cleaving the BBB, such that an increase in matrix metalloproteinase expression results in increased BBB permeability . Furthermore, in vitro studies have demonstrated a role for TERT in matrix metalloproteinase regulation in gliomas …”

Section: Discussionmentioning

confidence: 99%

“…23 Furthermore, in vitro studies have demonstrated a role for TERT in matrix metalloproteinase regulation in gliomas. 24 In addition to telomere preservation, TERT has been shown to upregulate matrix metalloproteinases, which are known to target the BBB. We, therefore, sought to evaluate BBB dysfunction in GBM in the context of TERT mutation.…”

Section: Discussionmentioning

confidence: 99%

MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

Ivanidze

Lum

Pisapia

et al. 2019

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Telomerase reverse transcriptase (TERT) promoter mutations are associated with worse prognosis in glioblastoma. The purpose of this study was to evaluate whether TERT mutation status was associated with specific morphologic and quantitative imaging features. METHODS Twenty‐nine patients with isocitrate dehydrogenase 1/2‐wildtype glioblastoma (13 TERT‐wildtype, 16 TERT‐mutated), who underwent preoperative magnetic resonance (MR) imaging were included in this retrospective study. Qualitative imaging phenotypes were evaluated using the Visually Accessible Rembrandt Images (VASARIs) feature set. Histogram analysis of apparent diffusion coefficient (ADC) and dynamic contrast‐enhanced MR perfusion values were performed on enhancing tumor volumes‐of‐interest, and differences between TERT‐wildtype and TERT‐mutated tumors were assessed. RESULTS VASARI analysis demonstrated that the majority of morphologic features were not significantly different between TERT‐wildtype and TERT‐mutated tumors, although a higher proportion of TERT‐wildtype tumors featured nonenhancing tumor crossing midline (P = .014). TERT‐mutated tumors demonstrated lower median rate constant kep (.38 vs. .76, P = .03) and lower median volume transfer coefficient Ktrans (.13 vs. .31, P = .02). There was no significant difference in median plasma volume vp (P = .92) or ADC values (P = .66) between the two groups. We further found a significant interaction between median kep and Ktrans and TERT status, respectively, suggesting greater risk of death with increasing blood‐brain barrier dysfunction in TERT‐mutated but not in TERT‐wildtype tumors. CONCLUSION Our study demonstrates evidence of altered permeability metrics associated with TERT mutation in glioblastoma, laying the foundation for future prospective studies assessing implications for therapeutic management and clinical outcomes.

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PinX1 inhibits cell proliferation, migration and invasion in glioma cells

Cited by 10 publications

References 29 publications

Naphthalene diimide‐derivatives G‐quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells

Naphthalene diimide‐derivatives G‐quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells

The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway

MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

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