Malignant mesothelioma (MM) is an aggressive tumor with a dismal prognosis, and the molecular alterations involved in this disease remain unknown. We previously reported that microRNA-34s (miR-34s) are methylated and downregulated in MM and may play an important role in the carcinogenesis of MM. In this study, we downregulated miR-34s in human mesothelial cells to investigate the cellular effect of miR-34 knockdown. For the cell study, we used LP-9, a human mesothelial cell line, and three human primary-cultured mesothelial cell lines. RNA-based miR-34a, -34b and -34c inhibitors were transfected into these cells, and their effects on proliferation and invasion were evaluated. A scramble RNA oligonucleotide was used as a control. The protein expression status was estimated using western blotting. After miR-34 inhibitor transfection, miR-34a, -34b and -34c were downregulated in all the examined mesothelial cell lines. miR-34 inhibitor transfection significantly increased cell proliferation in all of the mesothelial cell lines, compared with the scramble control. The invasive ability also increased in the miR-34 inhibitor transfectants, compared with the scramble control, in the LP-9 cell line. Western blotting confirmed the upregulation of c-MET, phospho-c-MET, and bcl-2 proteins in LP-9 cells after miR-34 inhibitor transfection. In conclusion, our study showed that the downregulation of miR-34s induced an oncogenic phenotype in non-malignant mesothelial cells. The present study, together with the results of our previous report, strongly suggest that miR-34s play an important role in the early carcinogenic process involved in the transformation of human mesothelial cells to MM.
microRNA - Wikipedia
A comparison between the effects of over-expression of miRNA-16 and miRNA-34a on cell cycle progression of mesothelioma cell lines and on their cisplatin sensitivity - ScienceDirect
Frontiers MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic
Frontiers MicroRNA as an Important Target for Anticancer Drug Development
Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma - ScienceDirect
IJERPH, Free Full-Text
Frontiers MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review
Restoring microRNA-34a overcomes acquired drug resistance and disease progression in human breast cancer cell lines via suppressing the ABCC1 gene
miR‐30d is related to asbestos exposure and inhibits migration and invasion in NCI‐H2452 cells - Ju - 2017 - FEBS Open Bio - Wiley Online Library
The P53/microRNA network: A potential tumor suppressor with a role in anticancer therapy - ScienceDirect
IJMS, Free Full-Text
Frontiers Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy
Onco, Free Full-Text
PDF) Promising therapeutic potential of tumor suppressor microRNAs for malignant pleural mesothelioma
Full article: MicroRNA-5195-3p plays a suppressive role in cell proliferation, migration and invasion by targeting MYO6 in human non-small cell lung cancer
