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.

An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer

“… 19 miR-21 regulates cell proliferation and migration by targeting PTEN and p53 in BC. 20 miR-202, 21 miR-212, 22 miR-222, 23 miR-429, 24 miR-200, 25 miR-210, 26 miR-214, 27 miR-182, 28 miR-99a, 29 miR-100 30 and miR-138 31 were reported in BC studies, which were mostly dependent on cell lines. The studies on miRNA relationship with BC survival were insufficient.…”

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

“…Owing to these findings’ paclitaxel can be used as a therapeutic approach in synergy with geridonim for gastric as well as bladder cancer. In bladder cancer, pacliaxel up-regulates the expression of miR-143 which post-transcriptionally inhibits the expression of Akt [ 134 ].…”

Relations between approved platinum drugs and non-coding RNAs in mesothelioma

“…Another tumor suppressor of MPM is represented by miR-145, which is lost in MPM and acts by downregulation of OCT4 and ZEB1 [86]. Cisplatin and paclitaxel upregulated the miR-145 level in bladder cancer cells while miR-145 expression sensitized gallbladder cancer to cisplatin by MRP1 suppression [87,88]. In contrast to that, miR-17–5p expression was high in short survivors of MPM and suppression of miR-17–5p targeting p21 led to increased cisplatin sensitivity of gastric cancer cells [23,89].…”

“…It was observed that cisplatin treatment led to the induction of tumor suppressor miRNAs (let-7c, miR-34a, miR-145, miR-451) and suppression of oncomirs (miR-210) and, thus, cisplatin can potentiate the efficacy of other chemotherapeutic drugs which depend significantly on the regulation of these miRNAs (Fig. 4) [44,61,87,88].

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