scholarly journals ITGA5 Predicts Dual-Drug Resistance to Temozolomide and Bevacizumab in Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Shi ◽  
Mengwan Wu ◽  
Yuyang Liu ◽  
Lanlin Hu ◽  
Hong Wu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Periodic Acid ◽  
Resistant Cell ◽  
Gene Expression Omnibus ◽  
Resistant Cell Line ◽  
The Cancer Genome Atlas ◽  
Expression Change ◽  
Periodic Acid Schiff ◽  
Genome Atlas

AimsAnti-angiotherapy (Bevacizumab) is currently regarded as a promising option for glioma patients who are resistant to temozolomide (TMZ) treatment. But ongoing clinical research failed to meet therapeutic expectations. This study aimed to explore the pivotal genetic feature responsible for TMZ and Bevacizumab resistance in glioma patients.MethodsWe downloaded the transcriptomic and methylation data of glioma patients from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases and grouped these patients into resistant and non-resistant groups based on their clinical profiles. Differentially expressed genes and pathways were identified and exhibited with software in R platform. A TMZ-resistant cell line was constructed for validating the expression change of the candidate gene, ITGA5. An ITGA5-overexpressing cell line was also constructed to investigate its biological function using the CCK8 assay, Western blot, periodic acid–Schiff (PAS) staining, and transcriptional sequencing.ResultsChange of the cell morphology and polarity was closely associated with TMZ mono-resistance and TMZ/Bevacizumab dual resistance in glioma patients. The expression level of ITGA5 was effective in determining drug resistance and the outcome of glioma patients, which is regulated by methylation on two distinct sites. ITGA5 was augmented in TMZ-resistant glioma cells, while overexpressing ITGA5 altered the cell-promoted TMZ resistance through enhancing vascular mimicry (VM) formation correspondingly.ConclusionsBoth the epigenetic and transcriptional levels of ITGA5 are effective in predicting TMZ and Bevacizumab resistance, indicating that ITGA5 may serve as a predictor of the treatment outcomes of glioma patients.

Lentivirus-mediated RNA interference reversing the drug-resistance in MDR1 single-factor resistant cell line K562/MDR1

2009 ◽  
Vol 33 (8) ◽  
pp. 1114-1119 ◽  
Author(s):  
Xueshi Ye ◽  
Ting Liu ◽  
Yuping Gong ◽  
Bohui Zheng ◽  
Wentong Meng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Rna Interference ◽  
Cell Line ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Single Factor

Establishment of Paclitaxel-Resistant Cell Line and the Underlying Mechanism on Drug Resistance

2012 ◽  
pp. 1 ◽  
Author(s):  
Jingjing Zhang ◽  
Jin Zhao ◽  
Wenjing Zhang ◽  
Guanyuan Liu ◽  
Dongmei Yin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Underlying Mechanism ◽  
Resistant Cell ◽  
Resistant Cell Line

scholarly journals The Significance of MicroRNAs Expression in Regulation of Extracellular Matrix and Other Drug Resistant Genes in Drug Resistant Ovarian Cancer Cell Lines

2020 ◽  
Vol 21 (7) ◽  
pp. 2619 ◽  
Author(s):  
Dominika Kazmierczak ◽  
Karol Jopek ◽  
Karolina Sterzynska ◽  
Barbara Ginter-Matuszewska ◽  
Michal Nowicki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Matrix ◽  
Drug Resistance ◽  
Cell Line ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Drug Resistant ◽  
Resistant Genes

Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high mortality is the development of drug resistance. It can be related to increased expression of drug transporters and increased expression of extracellular matrix (ECM) proteins. Our foremost aim was to exhibit alterations in the miRNA expression levels in cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP)—resistant variants of the W1 sensitive ovarian cancer cell line—using miRNA microarray. The second goal was to identify miRNAs responsible for the regulation of drug-resistant genes. According to our observation, alterations in the expression of 40 miRNAs were present. We could observe that, in at least one drug-resistant cell line, the expression of 21 miRNAs was upregulated and that of 19 miRNAs was downregulated. We identified target genes for 22 miRNAs. Target analysis showed that miRNA regulates key genes responsible for drug resistance. Among others, we observed regulation of the ATP-binding cassette subfamily B member 1 gene (ABCB1) in the paclitaxel-resistant cell line by miR-363 and regulation of the collagen type III alpha 1 chain gene (COL3A1) in the topotekan-resistant cell line by miR-29a.

scholarly journals Analysis of Candidate Idarubicin Drug Resistance Genes in MOLT-3 Cells Using Exome Nuclear DNA

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 390
Author(s):  
Tomoyoshi Komiyama ◽  
Atsushi Ogura ◽  
Takehito Kajiwara ◽  
Yoshinori Okada ◽  
Hiroyuki Kobayashi
Keyword(s):  
Drug Resistance ◽  
Amino Acid ◽  
Acute Leukemia ◽  
Cell Line ◽  
Nuclear Dna ◽  
Leukemia Cell ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Leukemia Cell Line ◽  
Amino Acid Mutations

Various gene alterations related to acute leukemia are reported to be involved in drug resistance. We investigated idarubicin (IDR) resistance using exome nuclear DNA analyses of the human acute leukemia cell line MOLT-3 and the derived IDR-resistant cell line MOLT-3/IDR. We detected mutations in MOLT-3/IDR and MOLT-3 using both Genome Analysis Toolkit (GATK) and SnpEff program. We found 8839 genes with specific mutations in MOLT-3/IDR and 1162 genes with accompanying amino acid mutations. The 1162 genes were identified by exome analysis of polymerase-related genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) and, among these, we identified genes with amino acid changes. In resistant strains, LIG and helicase plurality genes showed amino-acid-related changes. An amino acid mutation was also confirmed in polymerase-associated genes. Gene ontology (GO) enrichment testing was performed, and lipid-related genes were selected from the results. Fluorescent activated cell sorting (FACS) was used to determine whether IDR permeability was significantly different in MOLT-3/IDR and MOLT-3. The results showed that an IDR concentration of 0.5 μg/mL resulted in slow permeability in MOLT-3/IDR. This slow IDR permeability may be due to the effects of amino acid changes in polymerase- and lipid-associated genes.

scholarly journals Molecular mechanism of acquired drug resistance in the EGFR‐TKI resistant cell line HCC827‐TR

2020 ◽  
Vol 11 (5) ◽  
pp. 1129-1138
Author(s):  
Tao Yu ◽  
Qian Xia ◽  
Ting Gong ◽  
Jing Wang ◽  
DianSheng Zhong
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Molecular Mechanism ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Acquired Drug Resistance ◽  
Egfr Tki

scholarly journals Misregulation of translation drives prostate cancer drug resistance

2021 ◽  
Author(s):  
Emeline I. J. Lelong ◽  
France Hélène Joncas ◽  
Pauline Adjibade ◽  
Valerie ST.-Sauveur Grenier ◽  
Jean-Philippe Lambert ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cell Line ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Cancer Drug ◽  
Biological Processes ◽  
Drug Resistant ◽  
Cancer Resistance ◽  
Resistant Cells

ABSTRACTEmerging evidence associates translation factors and regulators to tumorigenesis. Recent advances in our ability to perform global translatome analyses indicate that our understanding of translational changes in cancer resistance is still limited. Here, we characterize global translational changes that occur during the acquisition of prostate cancer (PCa) drug resistance. We generated a patient derived xenograft (PDX) model created from PCa cells to recapitulate key features of resistant PCa progression. From an enzalutamide-sensitive patient derived cell line (VCaP), we generated a castration resistant cell line (VCaPCRPC) and an enzalutamide resistant cell line (VCaPER). We performed Total and polyribosome-bound RNA sequencing and mass spectroscopy from both VCaPCRPC and VCaPER to reveal their respective translatomes. We found that in drug-resistant cells, RNAs associated to ribosomes were enriched for nuclear RNA and DNA binding related biological processes, whereas RNAs that are less associated showed enrichment for processes such as cell membrane and cell-cell junction related biological processes. These results were corroborated by mass spectrometry and suggest that translation is indeed affected during drug resistance. Furthermore, our analysis revealed enrichment of long non-coding RNAs associated to ribosomes, which may suggest aberrant translation or translation of novel peptides that can be considered as new biomarkers. Our findings thus point towards novel therapeutic avenues that may target drug-resistant cells.

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