Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI

Yang, Yi; Chien, Yueh; Chiou, Guang-Yuh; Cherng, Jong Yuh; Wang, Mong‐Lien; Lo, Wen-Liang; Chang, Yuh Lih; Huang, Pin I.; Chen, Yi Wei; Shih, Yang Hsin; Chen, Ming Teh; Chiou, Shih Hwa

doi:10.1016/j.biomaterials.2011.10.071

Cited by 217 publications

(131 citation statements)

References 54 publications

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“…There were no significant differences between the two groups in terms of gender, age, international prognostic index (IPI) and stage. We investigated the pretreatment concentrations of serum miR-155, miR-200c, miR-29c, miR-130a, miR-145, miR-451, miR-125b and miR-21 expression levels, which have been reported in certain other tumor types to be associated with chemotherapy resistance (Table III) (9,14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). We observed that only the expression of miR-130a and miR-125b was correlated significantly with the response to chemotherapy.…”

Section: Dysregulated Expression Profiles Of Eight Mirnas In Dlbclmentioning

confidence: 90%

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Yuan

Gui

et al. 2015

Oncology Letters

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Abstract. Numerous studies have reported the aberrant expression profiles of microRNAs (miRNAs) in diffuse large B-cell lymphoma (DLBCL), although very few of these studies were concerned with chemoresistance to R-CHOP in DLBCL patients. This study was designed to assess the correlation between circulating miRNA expression and chemoresistance and prognosis in DLBCL patients. At the start of the study, we demonstrated that miRNA expression levels in serum were significantly associated with those in formalin-fixed, paraffin-embedded tissues, which indicated that circulating miRNAs may be powerful, non-invasive biomarkers reflecting miRNAs levels isolated from tumor tissue. Then from eight potential drug-resistant miRNAs which were deregulated in DLBCL and which had been reported to be associated with drug resistance in other carcinomas, we screened out the circulating miR-125b and miR-130a, which may related to R-CHOP resistance. Dynamic monitoring of the levels of circulating miR-125b and miR-130a further demonstrated that they were involved in recurrence, progression and chemoresistance in DLBCL patients. Finally, we demonstrated that high miR-125b indicated poor prognosis, as patients with higher miR-125b levels had a shorter overall survival. To our knowledge, this is the first study demonstrating that miR-125b and miR-130a are associated with the risk of chemoresistance in DLBCL patients, and that dynamic monitoring of the levels of circulating miR-125b and miR-130a predicts the therapeutic response and disease status of DLBCL patients.

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Section: Dysregulated Expression Profiles Of Eight Mirnas In Dlbclmentioning

confidence: 90%

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Yuan

Gui

et al. 2015

Oncology Letters

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“…The product, PU-PEI600-maleimide, was also characterized by FTIR and 1 H NMR. 1 H NMR (400 MHz, D2O, ppm) δ: 0.95 (-NHCH2CH2NH-), 1,21-1.81 (6H, -CH(COOCH3)CH2CH2CH2CH2-), 2.0 (-CONHCH2CH2-), 2.48, 3.14 (-NHCH2CH2NH-), 2.50-2.71 (-N2(CH2CH2)2), 2.90 (-CH2CH2NH-), 2.94, 4.02 (-COCH2CH2N(CO-)2), 2.99, 3.9 (-NCH2CH2O-), 3.12 (-NHCH(COOCH3)CH2-), 3.51 (-CH2NHCOOCH3), 3.67 (-NHCOOCH3), 3.8 (-CONHCH2CH2-), 5.05 (-CH2CH2NHCOCH2CH2-), 8.01 (-NHCH(COOCH3)CH2-), 8.22 (-COCH=CHCO-). Also shown in Scheme 1, PU-PEI 600 was synthesized using the aminolysis reaction of PU and small molecular weight polyethylenimine (M w = 600, PEI 600 ).…”

Section: Synthesis Pu-pei600-maleimidementioning

confidence: 99%

“…The optimum of designing synthetic gene delivery vehicles is to build DNA/vehicle assemblies that are biocompatible and efficient enough to be used in human therapy. In our previous reports, cationic polyurethane exhibited high transfection efficiency with relatively low cytotoxicity in vitro and in vivo [2,3]. A high molecular weight polyethylenimine (PEI 25k , M w~2 5,000) revealed its highly effective potential among vectors based on cationic polymers because of its ability of prominent endolysosomal escape and its character of structural protonation [4].…”

Section: Introductionmentioning

confidence: 98%

Maleimide-Functionalized PEI600 Grafted Polyurethane: Synthesis, Nano-Complex Formation with DNA and Thiol-Conjugation of the Complexes for Dual DNA Transfection

Hung

Cherng

2015

Polymers

Self Cite

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Abstract:A polyurethane (PU) grafted with small molecular weight polyethylenimine (PEI 600 ) was synthesized. This PU-PEI 600 can assemble DNA via electrostatic interactions into nano-sized polymer/DNA complexes. The complexes exhibited great transfection efficiency in delivering DNA along with a reduced cell toxicity comparing to commercial PEI 25k (M w~2 5,000). In order to establish a system for concurrently delivering two different DNA or RNA molecules for cell reprogramming (e.g., induced pluripotent stem cells) or the necessity of multi-expression (e.g., double knock down), the PU-PEI 600 was further functionalized with maleimide molecules. The novel PU-PEI 600 -maleimide would still effectively interact with assigned DNA and different functions of PU-PEI 600 -maleimide/DNA complexes were self-conjugated in presence of a dithiol molecule (1,6-hexanedithiol). In this study, two reporter genes (pEGFP-C2 and pLanRFP-N) were used and evidence of green/red fluorescence co-expression in cells was observed. This article brings a new concept and a practical method for a plurality of different DNA molecules that are more efficient to be concurrently delivered and co-expressed. This method is very helpful in studying cellular multi-regulation or in the treatment of disease with multiple gene defects in vivo.

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“…Noteworthy, it has been reported that DDX6 upregulates tumorigenicity in colon cancer. Moreover, upregulation of DDX6 decreases miR-145 expression and induces tumorigenicity in GBM (38,39). Yet, our studies show that DDX6 induces RT/TMZ resistance rather than tumorigenic ability or miRNA modulation.…”

Section: Discussionmentioning

confidence: 52%

Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma

Cho

Kang

Kim

et al. 2016

International Journal of Oncology

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Abstract. CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio-and chemoresistance in GBM.

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Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI

Cited by 217 publications

References 54 publications

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Maleimide-Functionalized PEI600 Grafted Polyurethane: Synthesis, Nano-Complex Formation with DNA and Thiol-Conjugation of the Complexes for Dual DNA Transfection

Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma

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