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. 2016 Apr 26;7(3):340-7.
doi: 10.1111/1759-7714.12336. Epub 2016 Jan 31.

Overexpression of micro ribonucleic acid-591 inhibits cell proliferation and invasion of malignant pleural mesothelioma cells

Shizhao Cheng  1 , Yue Xu  2 , Zhenliang Shi  3 , Yongbin Lin  4 , Chuong D Hoang  2 , Xun Zhang  3
Affiliations

Overexpression of micro ribonucleic acid-591 inhibits cell proliferation and invasion of malignant pleural mesothelioma cells

Shizhao Cheng et al. Thorac Cancer. .

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer refractory to current therapies. Reduced expression of micro ribonucleic acid (miR)-591 in a range of cancer types has suggested it is a potent tumor suppressor, and overexpression has been shown to inhibit tumor cell growth. The role of miR-591 in MPM is largely unknown.

Methods: miR-591 was over-expressed in vitro using micro RNA mimics in three MPM cell lines (H513, H2052, H2373), and effects on tumor cell growth, proliferation, invasion, and target gene expression were assessed.

Results: miR-591 mimic was introduced into MPM cell lines to overexpress this microRNA. The cellular growth, proliferation, and invasive capability was significantly inhibited after overexpression of miR-591. Growth inhibition caused by miR-591 correlated with upregulation of p21 and Bax. Reduced invasive capability correlated with downregulation of matrix metalloproteinase-2 and transforming growth factor-β1.

Conclusion: miR-591 is a potent tumor suppressor in MPM. Overexpression of miR-591 may represent a novel therapeutic approach for MPM.

Keywords: Malignant pleural mesothelioma; miR‐591; microRNA.

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Figures

Figure 1
Figure 1
Growth effects of micro ribonucleic acid (miR)‐591 overexpression in mesothelioma cell lines. (a) Crystal violet staining of cells on day three post‐transfection of miR‐591. Decreased cell growth was observed in miR‐591‐transfected cells (miR‐591) compared with a scrambled control. Magnification, 40x. (b) Quantitative analysis of the staining assay indicated significant changes (P < 0.05). *Indicates significant change (P < 0.05). OD, optical density, measured in this assay as a correlate of a number of viable cells. formula image, Control; formula image, miR‐591.
Figure 2
Figure 2
XTT growth assay. Significantly decreased cell proliferation was observed in micro ribonucleic acid (miR)‐591‐transfected cells (miR‐591) compared with a scrambled control by days three and six in all three MPM cell lines. *Indicates significant change (P < 0.05). OD, optical density, measured in this assay as a correlate of a number of viable cells. formula image, miR‐591; formula image, Control.
Figure 3
Figure 3
Transwell assay. Micro ribonucleic acid (miR)‐591 suppressed tumor cell invasive capability in vitro. (a) Representative images of the transwell assay of H513, H2052, and H2373 after transfection with miR‐591 or a scrambled control. Magnification, 100x. (b) Quantitative analysis of the transwell assay indicated significant changes (P < 0.05). *Indicates significant change (P < 0.05).
Figure 4
Figure 4
Gene expression changes associated with the growth arrest phenotype in micro ribonucleic acid (miR)‐591 transfected mesothelioma cells. Significant increases in P21 and BAX were observed in miR‐591‐transfected cells compared with a scrambled control. Fold changes were calculated by the ΔΔCt method. *Indicates significant change (P < 0.05). formula image, Control; formula image, miR‐591.
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