Inhibition of miR‑18a‑3p reduces proliferation of mesothelioma cells and sensitizes them to cisplatin

Abstract

Malignant pleural mesothelioma is a notorious human malignancy. Despite combination chemotherapy with cisplatin and pemetrexed, the majority of patients with advanced malignant pleural mesothelioma have a poor prognosis. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that regulate various biological processes by binding to the 3'-untranslated region of target gene mRNAs and suppressing their expression. Since abnormal expression patterns of miRNAs are a common feature in human malignancies, a number of them have been researched as potential therapeutic targets. Our previous study demonstrated that microRNA-18a (miR-18a) is upregulated in mesothelioma cell lines compared with in non-neoplastic mesothelial tissues, but its function remains unclear. In the present study, miRNA inhibitor was transfected into mesothelioma cell lines and then analyzed various cellular functions. Mesothelioma cells transfected with the miR-18a inhibitor exhibited lower proliferation and migration rates compared with cells transfected with a negative control inhibitor in proliferation and wound scratch assays, respectively. Additionally, the present study revealed that downregulation of miR-18a increased mesothelioma cell apoptosis. In a chemosensitivity assay, transfection of the miR-18a inhibitor significantly increased the sensitivity of mesothelioma cells to cisplatin but not to pemetrexed. Therefore, miR-18a may be a potential therapeutic target for mesothelioma resistant to cisplatin. Materials and methods Mesothelioma cell lines. Four human mesothelioma cell lines were used in this study. Two cell lines (ACC-MESO1 and ACC-MESO4) were purchased from the RIKEN BioResearch Center (Tsukuba, Japan) (15) and the other two (CRL-5915 and CRL-5946) were purchased from the American Type Culture Collection. Cells were cultured with Roswell Park Memorial

miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV

“…To develop therapies for malignant mesothelioma, ncRNAs have recently gained attention as a therapeutic target [5]. Although ncRNAs do not produce proteins as the final product, it is gradually becoming evident in our laboratory that ncRNAs have an underlying influence on the molecular mechanisms of malignant mesothelioma [29-31]. This study suggests ncRNA as a potential therapeutic target by using molecular biological methods using mesothelioma cell lines.…”

Tumor-Educated Platelet miR-18a-3p as a Novel Liquid-Biopsy Biomarker for Early Diagnosis and Chemotherapy Efficacy Monitoring in Nasopharyngeal Carcinoma

“…MicroRNAs are short non-coding single-stranded RNA that regulates gene expression by binding to complementary sequences in 3 or 5 untranslated region of target gene mRNA. Some studies have reported that MicroRNAs may play an important role in the pathogenesis of various human cancers (19). MicroRNAs can induce abnormal metabolism of tumor cells by affecting the process of transcription and translation of tumor cells.…”

“…The chemotherapy schemes included paclitaxel combined with cisplatin, gemcitabine combined with cisplatin. Suzuki reported that inhibition of miR-18a-3p reduced proliferation of mesothelioma cells and sensitizes them to cisplatin (19), Rodriguez-Aguayo reported that miR-18a-3p was related to chemotherapy-resistant ovarian cancer (26).…”

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

“…Downregulation of miR-31 was observed in epithelioid MM versus non-epithelioid MM. Patients with BAP1 loss/low miR-31 combination had a better prognosis; hence, this was seen as an independent prognostic factor for epithelioid-MPM patients [ 47 ]. The BAP1 mutation-specific miRNA signature has previously been identified as prognostic biomarkers in other cancers as well [ 73 ] whilst BAP1 alone could not be correlated with clinical outcomes [ 74 , 75 ].…”