Dataset Information

Cisplatin and Paclitaxel Alter the Expression Pattern of miR-143/145 and miR-183/96/182 Clusters in T24 Bladder Cancer Cells.

ABSTRACT: Although cisplatin-based chemotherapy is considered to be the treatment of choice for metastatic bladder cancer, its efficacy and tolerability has proven to be limited. MicroRNAs are small noncoding RNAs, whose genes are frequently organized in clusters. These molecules constitute posttranscriptional regulators of mRNA expression and are claimed to be deregulated in cancer. miR-143/145 and miR-183/96/182 clusters have been extensively studied in bladder cancer cells. Herein, we tried to add up to this knowledge by assessing the expression levels of the five mature microRNAs derived from the aforementioned clusters in T24 bladder cancer cells exposed to either cisplatin or paclitaxel. For both compounds, the viability of treated T24 cells was estimated via the MTT colorimetric assay and the Trypan Blue exclusion method, while a fraction of the cells was left to recover. The expression levels of all mature microRNAs were finally quantified both in treated and in recovered cells by performing real-time PCR. According to our data, cisplatin and paclitaxel strongly decreased T24 cells' viability, showing in parallel the ability to significantly down-regulate miR-143 levels, and up-regulate the expression levels of miR-145, miR-183, miR-96, and miR-182, which, in their total, demonstrated case-specific variations after recovery period.

SUBMITTER: Papadopoulos EI

PROVIDER: S-EPMC5351132 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Cisplatin and Paclitaxel Alter the Expression Pattern of miR-143/145 and miR-183/96/182 Clusters in T24 Bladder Cancer Cells.

Papadopoulos Emmanuel I EI Scorilas Andreas A

Clinical and translational science 20150910 6

Although cisplatin-based chemotherapy is considered to be the treatment of choice for metastatic bladder cancer, its efficacy and tolerability has proven to be limited. MicroRNAs are small noncoding RNAs, whose genes are frequently organized in clusters. These molecules constitute posttranscriptional regulators of mRNA expression and are claimed to be deregulated in cancer. miR-143/145 and miR-183/96/182 clusters have been extensively studied in bladder cancer cells. Herein, we tried to add up t ...[more]

PMID: 26356996

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Project description:Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt's lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to EBV nuclear antigen 1 (EBNA1), but small noncoding RNAs such as EBV-encoded small RNAs (EBERs) and microRNAs (miRNAs) can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation, and cell death. It has recently become clear that alterations in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small-RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to Northern blotting and real-time reverse transcription-PCR (RT-PCR) analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BamHI A rightward transcript (miR-BART) cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since transforming growth factor ?1 (TGF-?1) stimulation did not significantly change the miRNA profiles. However, using several approaches, including de novo infection with a mutant virus, we present evidence that the expression of latent membrane protein 1 (LMP-1) triggered downregulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the Akt signaling pathway.In addition to expressing their own miRNAs, herpesviruses also impact the expression levels of cellular miRNAs. This regulation can be either positive or negative and usually results in the perturbation of pathways to create a cellular environment that is more "virus-friendly." For example, EBV induces the expression of miR-155, a well-characterized oncomiR, which leads to increased cell proliferation and decreased cell death. Here, we show that EBV-encoded LMP-1 is also involved in the downregulation of a cluster of three miRNAs, miR-183, -96, and -182, which are known to be also repressed in several cancers. We therefore identify yet another potential player in EBV-induced oncogenesis.

Dataset Information

Cisplatin and Paclitaxel Alter the Expression Pattern of miR-143/145 and miR-183/96/182 Clusters in T24 Bladder Cancer Cells.

Publications

Cisplatin and Paclitaxel Alter the Expression Pattern of miR-143/145 and miR-183/96/182 Clusters in T24 Bladder Cancer Cells.

Similar Datasets

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