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MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1.

Gu Y, Cheng Y, Song Y, Zhang Z, Deng M, Wang C, Zheng G, He Z - PLoS ONE (2014)

Bottom Line: Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma.The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo.Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR China; Medical School, University of South China, Hengyang, Hunan, PR China.

ABSTRACT
miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.

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miR-493 inhibits the proliferation and invasion of lung cancer cells by targeting E2F1.A, The knock-down of E2F1 partly simulated the suppression lung cancer cells growth induced by the overexpression of miR-493 in 95D and H1975 cells. The growth curves demonstrated the capability of lung cells proliferation. The absorption value of cells was measured at the indicated time points in triplicate and their growth rates were recorded. B, Overexpression of exogenous E2F1 (without 3′-UTR of E2F1) rescued upon the proliferation suppression induced by miR-493 in 95D and H1975 cells. C, T The invasive properties of H1975 and 95D cells which were either knock-down or overexpression of E2F1were analyzed with a transwell assay using a Matrigel-coated chamber. The migrated cells were plotted as the average number of cells per field of view from 3 different experiments, as described in the Materials and Methods. The data are the mean ± SD.* means p<0.05. D and E, Representative images of the assays are shown. Original magnification: ×200.
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pone-0102602-g005: miR-493 inhibits the proliferation and invasion of lung cancer cells by targeting E2F1.A, The knock-down of E2F1 partly simulated the suppression lung cancer cells growth induced by the overexpression of miR-493 in 95D and H1975 cells. The growth curves demonstrated the capability of lung cells proliferation. The absorption value of cells was measured at the indicated time points in triplicate and their growth rates were recorded. B, Overexpression of exogenous E2F1 (without 3′-UTR of E2F1) rescued upon the proliferation suppression induced by miR-493 in 95D and H1975 cells. C, T The invasive properties of H1975 and 95D cells which were either knock-down or overexpression of E2F1were analyzed with a transwell assay using a Matrigel-coated chamber. The migrated cells were plotted as the average number of cells per field of view from 3 different experiments, as described in the Materials and Methods. The data are the mean ± SD.* means p<0.05. D and E, Representative images of the assays are shown. Original magnification: ×200.

Mentions: In addition, we constructed siRNA fragments targeting E2F1 to knock down the expression of E2F1 to investigate the contribution of E2F1 to the effect of miR-493 on these phenotypes. We found that the knockdown E2F1 could partly simulation the cell growth (figure 5 B) and cell invasion (figure 5C and D) phenotype induced by the overexpression of miR-493. Subsequently, rescue experiments were performed by overexpressing the E2F1-Δ3′- UTR vector (without an endogenous 3′- UTR) in cell expressing miR-493. The miR-493 induced downregulation of E2F1 was rescued upon the introduction of E2F1. Moreover, the overexpression of E2F1 attenuated the inhibition of cell growth (figure 5A) and invasion (figure 5C and E) caused by miR-493. These observations suggest that miR-493 specifically targets E2F1 specificity to contribute to the effect of on cell growth and invasion.


MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1.

Gu Y, Cheng Y, Song Y, Zhang Z, Deng M, Wang C, Zheng G, He Z - PLoS ONE (2014)

miR-493 inhibits the proliferation and invasion of lung cancer cells by targeting E2F1.A, The knock-down of E2F1 partly simulated the suppression lung cancer cells growth induced by the overexpression of miR-493 in 95D and H1975 cells. The growth curves demonstrated the capability of lung cells proliferation. The absorption value of cells was measured at the indicated time points in triplicate and their growth rates were recorded. B, Overexpression of exogenous E2F1 (without 3′-UTR of E2F1) rescued upon the proliferation suppression induced by miR-493 in 95D and H1975 cells. C, T The invasive properties of H1975 and 95D cells which were either knock-down or overexpression of E2F1were analyzed with a transwell assay using a Matrigel-coated chamber. The migrated cells were plotted as the average number of cells per field of view from 3 different experiments, as described in the Materials and Methods. The data are the mean ± SD.* means p<0.05. D and E, Representative images of the assays are shown. Original magnification: ×200.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4126682&req=5

pone-0102602-g005: miR-493 inhibits the proliferation and invasion of lung cancer cells by targeting E2F1.A, The knock-down of E2F1 partly simulated the suppression lung cancer cells growth induced by the overexpression of miR-493 in 95D and H1975 cells. The growth curves demonstrated the capability of lung cells proliferation. The absorption value of cells was measured at the indicated time points in triplicate and their growth rates were recorded. B, Overexpression of exogenous E2F1 (without 3′-UTR of E2F1) rescued upon the proliferation suppression induced by miR-493 in 95D and H1975 cells. C, T The invasive properties of H1975 and 95D cells which were either knock-down or overexpression of E2F1were analyzed with a transwell assay using a Matrigel-coated chamber. The migrated cells were plotted as the average number of cells per field of view from 3 different experiments, as described in the Materials and Methods. The data are the mean ± SD.* means p<0.05. D and E, Representative images of the assays are shown. Original magnification: ×200.
Mentions: In addition, we constructed siRNA fragments targeting E2F1 to knock down the expression of E2F1 to investigate the contribution of E2F1 to the effect of miR-493 on these phenotypes. We found that the knockdown E2F1 could partly simulation the cell growth (figure 5 B) and cell invasion (figure 5C and D) phenotype induced by the overexpression of miR-493. Subsequently, rescue experiments were performed by overexpressing the E2F1-Δ3′- UTR vector (without an endogenous 3′- UTR) in cell expressing miR-493. The miR-493 induced downregulation of E2F1 was rescued upon the introduction of E2F1. Moreover, the overexpression of E2F1 attenuated the inhibition of cell growth (figure 5A) and invasion (figure 5C and E) caused by miR-493. These observations suggest that miR-493 specifically targets E2F1 specificity to contribute to the effect of on cell growth and invasion.

Bottom Line: Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma.The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo.Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR China; Medical School, University of South China, Hengyang, Hunan, PR China.

ABSTRACT
miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.

Show MeSH
Related in: MedlinePlus