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MiR-130a activates apoptotic signaling through activation of caspase-8 in taxane-resistant prostate cancer cells [total RNA]

ABSTRACT: Background: The acquisition of drug resistance is one of the most malignant phenotypes of cancer. MicroRNAs (miRNAs) have been implicated in various types of cancers, but its role in taxane-resistance of prostate cancer remains poorly understood. Methods: In order to identify miRNAs related to taxane-resistance, miRNA profiling was performed using prostate cancer PC3 cells and paclitaxel-resistant PC3 cell lines established from PC3 cells. Microarray analysis of mRNA expression was also conducted to search for potential target genes of miRNA. The effects of ectopic expression of miRNA on cell growth, tubulin polymerization, drug sensitivity and apoptotic signaling pathway were investigated in a paclitaxel-resistant PC3 cell line. Results: The expression of miR-130a was down-regulated in all paclitaxel-resistant cell lines compared with parental PC3 cells. Based on mRNA microarray analysis, we identified SLAIN1 and CAV2 as potential target genes for miR-130a. Transfection with a miR-130a precursor into a paclitaxel-resistant cell line suppressed cell growth and increased the sensitivity to paclitaxel. Lastly, ectopic expression of miR-130a did not affect the polymerized tubulin level, but activated apoptotic signaling through activation of caspase-8. Conclusion: These results suggested that miR-130a may be involved in the paclitaxel-resistance and could be a therapeutic target for taxane-resistant prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE64012 | GEO | 2015/07/31

SECONDARY ACCESSION(S): PRJNA269755

REPOSITORIES: GEO

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miR-130a activates apoptotic signaling through activation of caspase-8 in taxane-resistant prostate cancer cells [miRNA]

Project description:Background: The acquisition of drug resistance is one of the most malignant phenotypes of cancer. MicroRNAs (miRNAs) have been implicated in various types of cancers, but its role in taxane-resistance of prostate cancer remains poorly understood. Methods: In order to identify miRNAs related to taxane-resistance, miRNA profiling was performed using prostate cancer PC3 cells and paclitaxel-resistant PC3 cell lines established from PC3 cells. Microarray analysis of mRNA expression was also conducted to search for potential target genes of miRNA. The effects of ectopic expression of miRNA on cell growth, tubulin polymerization, drug sensitivity and apoptotic signaling pathway were investigated in a paclitaxel-resistant PC3 cell line. Results: The expression of miR-130a was down-regulated in all paclitaxel-resistant cell lines compared with parental PC3 cells. Based on mRNA microarray analysis, we identified SLAIN1 and CAV2 as potential target genes for miR-130a. Transfection with a miR-130a precursor into a paclitaxel-resistant cell line suppressed cell growth and increased the sensitivity to paclitaxel. Lastly, ectopic expression of miR-130a did not affect the polymerized tubulin level, but activated apoptotic signaling through activation of caspase-8. Conclusion: These results suggested that miR-130a may be involved in the paclitaxel-resistance and could be a therapeutic target for taxane-resistant prostate cancer.

2015-07-31 | GSE64013 | GEO

miR-130a activates apoptotic signaling through activation of caspase-8 in taxane-resistant prostate cancer cells [total RNA]

2015-07-31 | E-GEOD-64012 | biostudies-arrayexpress

miR-130a activates apoptotic signaling through activation of caspase-8 in taxane-resistant prostate cancer cells [miRNA]

2015-07-31 | E-GEOD-64013 | biostudies-arrayexpress

miRNA expression, mRNA expression upon miRNA reconstitution, and direct mRNA target identification in prostate cancer cell lines

Project description:This SuperSeries is composed of the following subset Series: GSE17315: mRNA expression upon reconstitution of miR-130a, miR-203 and miR-205 in prostate cancer cell line LNCaP GSE17317: miRNA expression in LNCaP, PC3, Du-145 and RWPE-1 cell lines GSE22979: Profiling of direct mRNA targets of miR-130a, miR-203 and miR-205 in prostate cancer cell line LNCaP Refer to individual Series

2012-03-07 | E-GEOD-17362 | biostudies-arrayexpress

Gene expression profiling of the prostate cancer cell line PC3.

Project description:To study the effect of miR-130a in prostate cancer, PC3 cells overexpressing miR-130a were analyzed for global gene expression.

2017-03-10 | GSE80750 | GEO

Downregulation of miR-194-5p induces paclitaxel resistance in ovarian cancer cells by altering MDM2 expression.

Project description:Paclitaxel is a first-line drug for treating epithelial ovarian cancer (EOC). However, prognosis for patients with advanced stage cancer remains poor due to primary or acquired drug resistance. Therefore, overcoming chemoresistance is one of the greatest challenges in treating EOC. In this study, we identified microRNAs (miRNA) that regulate paclitaxel resistance and tested their potential utility as therapeutic targets. Paclitaxel-resistant cell lines were established using two EOC cell lines: SKVO3ip1 and HeyA8. miRNA PCR arrays showed that miR-194-5p was downregulated in paclitaxel-resistant cells. Forced expression of miR-194-5p resensitized resistant cells to paclitaxel. Conversely, miR-194-5p inhibition induced paclitaxel resistance in parental cells. In silico analysis and luciferase reporter assay revealed that MDM2 is a direct target of miR-194-5p. MDM2 was upregulated in paclitaxel resistant cells compared with parental cells. MDM2 inhibition also resensitized resistant cells to paclitaxel and forced MDM2 induced paclitaxel resistance in parental cells. miR-194-5p induced p21 upregulation and G1 phase arrest in resistant cells by downregulating MDM2. Furthermore, a public database showed that high MDM2 expression was associated with a shorter progression-free survival in EOC patients treated with paclitaxel. Collectively, our results show that restoring miR-194-5p expression resensitizes EOCs to paclitaxel, and this may be exploited as a therapeutic option.

2019-10-18 | GSE139043 | GEO

Gene expression data of sensitive, Docetaxel resistant and Paclitaxel resistant MDA-MB-231 Cells

Project description:The taxanes, namely Paclitaxel and Docetaxel, are important and widely used cancer chemotherapy drugs in the treatment of invasive and metastatic human breast cancer. Although treatment with the taxanes is beneficial to many patients, drug-responsive tumors in patients with metastatic breast cancer often display resistance to these drugs, either initially or over time following the continued administration of chemotherapy drugs. To investigate the patterns of cross-resistance with the taxane drugs and to identify potential mechanisms of resistance, we generated a series of MDA-MB-231 taxane resistant cell lines. We then used microarrays to determine gene expression differences between sensitive, Docetaxel and Paclitaxel resistant MDA-MB-231 cells. RNA isolated from three independent passages of sensitive, Docetaxel and Paclitaxel resistant cell lines and purified using the Qiagen RNeasy Mini Kit. Total RNA was processed and hybridized to Affymetrix Genechip HU133A arrays.

2011-04-22 | E-GEOD-28784 | biostudies-arrayexpress

MicroRNA profiling in resistance ovarian cell lines

Project description:Although many genes associated with the development of resistance to chemotherapy are known, the mechanisms of their regulation are still poorly understood. One of the ways to regulate gene expression is regulation at mRNA level by small noncoding RNA particles – designated as a micro RNA (miRNA). Changes in miRNA expression were also observed in cell line studyes. Downregulation of miR-31 expression correlated with taxane resistance in ovarian cancer cell lines. In contrast upregulation of miR-98-5p was observed in cisplatin (CIS) -resistant cell lines. Changes in miRNAs expression were also noted in another cancers. miR-195 expression was downregulated in temozolomid-resistant glioma cells and miR-203 was downregulated in prostate cancer cells resistant to doxorubicin (DOX). The use of miRNA microarrays to analyse changes in miRNA gene expression is an effective molecular tool for the discovering new miRNA genes involved in drug resistance processes. The present study shows alterations in the miRNA expression levels in the CIS (W1CR), PAC (W1PR1 and W1PR2), DOX (W1DR), and topotecan (TOP) (W1TR) - resistant variants of W1 sensitive ovarian cancer cell line.

2020-04-08 | GSE148251 | GEO

Profiling of direct mRNA targets of miR-130a, miR-203 and miR-205 in prostate cancer cell line LNCaP

Project description:Micro RNAs (miRNAs) miR-130a, miR-203 and miR-205 are jointly downregulated in prostate cancer and act as repressors of AR-signaling. MiRNAs are small non-coding RNAs that regulate the expression of specific mRNA targets mainly by translational repression, mRNA deadenylation or cleavage. Reconstitution of these lost miRNAs in the LNCaP PCa cell line cause morphology changes, growth arrest, and apoptosis, increasing when the miRNAs were co-expressed. This series identifies direct targets of miR-130a, miR-203, and miR-205 by AGO2-RNA co-immunoprecipitation as described by (Beitzinger et al. 2007) upon miRNA reconstitution in LNCaP cells and analyzing AGO2-bound mRNAs using Affymetrix Genechips. Relative levels of AGO2 bound versus total RNA expression were compared between miRNA reconstituted and miR-scr transfected samples. Three arrays each for AGO2-bound RNA upon reconstitution of miR-130a, miR-203, miR-205, a scramble miRNA, and three arrays each for total RNA upon reconstitution of miR-130a, miR-203, miR-205, a scramble miRNA.

2012-03-08 | E-GEOD-22979 | biostudies-arrayexpress

Gene expression data of sensitive, Docetaxel resistant and Paclitaxel resistant MDA-MB-231 Cells

2011-04-22 | GSE28784 | GEO

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