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MicroRNA-140 Inhibits Cell Proliferation in Gastric Cancer Cell Line HGC-27 by Suppressing SOX4.

Zou J, Xu Y - Med. Sci. Monit. (2016)

Bottom Line: SOX4, a predicted target of miR-140, was mutated to verify its regulation by miR-140, and was overexpressed to analyze its function in cell proliferation.Doxorubicin treatment was performed to investigate the effect of miR-140 on drug resistance.Overexpressing SOX4 led to promoted cell viability, colony formation, and cell cycle progress. miR-140 overexpression also improved the anti-viability effects of doxorubicin, suggesting its potential in reducing the drug resistance of gastric cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (mainland).

ABSTRACT
BACKGROUND Gastric cancer is a malignant tumor with a high morbidity and mortality. MicroRNAs are important regulators of gene expression, influencing the progression of gastric cancer. This study aimed to reveal the role of microRNA-140 (miR-140) in gastric cancer cell proliferation and its potential mechanisms. MATERIAL AND METHODS Gastric cancer tissues and cell lines BGC-823, SGC-7901, and HGC-27 were used to analyze miR-140 levels compared to normal tissues and cell line GES-1. In HGC-27 cells transfected with miR-140 mimic, we performed MTT, colony formation assay, and cell cycle assay by flow cytometry. SOX4, a predicted target of miR-140, was mutated to verify its regulation by miR-140, and was overexpressed to analyze its function in cell proliferation. Doxorubicin treatment was performed to investigate the effect of miR-140 on drug resistance. RESULTS miR-140 was down-regulated in gastric cancer tissues and cell lines, with the lowest expression level in HGC-27. miR-140 overexpression inhibited HGC-27 cell viability and colony formation and resulted in G0/G1 arrest. miR-140 suppressed SOX4 expression via binding to the 3' untranslated region, while the mutant SOX4 could not be regulated. Overexpressing SOX4 led to promoted cell viability, colony formation, and cell cycle progress. miR-140 overexpression also improved the anti-viability effects of doxorubicin, suggesting its potential in reducing the drug resistance of gastric cells. CONCLUSIONS These findings suggest that miR-140 directly inhibits SOX4, which might be one of its mechanisms in suppressing gastric cancer cell proliferation. This study provides a promising therapeutic strategy for treating gastric cancer and facilitates microRNA research in various diseases.

No MeSH data available.


Related in: MedlinePlus

miR-140 leads to G0/G1 arrest of HGC-27 cells. (A) Flow cytometry results show the cell percent in the G0/G1 phase is increased, while that in S and G2/M phases is decreased by miR-140 overexpression. (B) Histogram reflects the cell cycle distribution in (A). (C) CCND1 and CDK2 mRNA levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. * P<0.05. (D) CCND1 and CDK2 protein levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. CCND1 – cyclin D1. CDK2 – cyclin-dependent kinase 2.
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f2-medscimonit-22-2243: miR-140 leads to G0/G1 arrest of HGC-27 cells. (A) Flow cytometry results show the cell percent in the G0/G1 phase is increased, while that in S and G2/M phases is decreased by miR-140 overexpression. (B) Histogram reflects the cell cycle distribution in (A). (C) CCND1 and CDK2 mRNA levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. * P<0.05. (D) CCND1 and CDK2 protein levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. CCND1 – cyclin D1. CDK2 – cyclin-dependent kinase 2.

Mentions: Since miR-140 was able to suppress cell proliferation, it was possible that its anti-proliferative role was related to the hindered cell cycle, which was to be investigated. Flow cytometry results showed that the percentage of HGC-27 cells in the G0/G1 phase was increased when miR-140 was overexpressed (Figure 2A, 2B), while cells in the S and G2/M phases were decreased, indicating that the HGC-27 cells overexpressing miR-140 were arrested in the G0/G1 phase compared to the mimic control.


MicroRNA-140 Inhibits Cell Proliferation in Gastric Cancer Cell Line HGC-27 by Suppressing SOX4.

Zou J, Xu Y - Med. Sci. Monit. (2016)

miR-140 leads to G0/G1 arrest of HGC-27 cells. (A) Flow cytometry results show the cell percent in the G0/G1 phase is increased, while that in S and G2/M phases is decreased by miR-140 overexpression. (B) Histogram reflects the cell cycle distribution in (A). (C) CCND1 and CDK2 mRNA levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. * P<0.05. (D) CCND1 and CDK2 protein levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. CCND1 – cyclin D1. CDK2 – cyclin-dependent kinase 2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4930272&req=5

f2-medscimonit-22-2243: miR-140 leads to G0/G1 arrest of HGC-27 cells. (A) Flow cytometry results show the cell percent in the G0/G1 phase is increased, while that in S and G2/M phases is decreased by miR-140 overexpression. (B) Histogram reflects the cell cycle distribution in (A). (C) CCND1 and CDK2 mRNA levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. * P<0.05. (D) CCND1 and CDK2 protein levels are inhibited by miR-140 overexpression. GAPDH is used as the internal control. CCND1 – cyclin D1. CDK2 – cyclin-dependent kinase 2.
Mentions: Since miR-140 was able to suppress cell proliferation, it was possible that its anti-proliferative role was related to the hindered cell cycle, which was to be investigated. Flow cytometry results showed that the percentage of HGC-27 cells in the G0/G1 phase was increased when miR-140 was overexpressed (Figure 2A, 2B), while cells in the S and G2/M phases were decreased, indicating that the HGC-27 cells overexpressing miR-140 were arrested in the G0/G1 phase compared to the mimic control.

Bottom Line: SOX4, a predicted target of miR-140, was mutated to verify its regulation by miR-140, and was overexpressed to analyze its function in cell proliferation.Doxorubicin treatment was performed to investigate the effect of miR-140 on drug resistance.Overexpressing SOX4 led to promoted cell viability, colony formation, and cell cycle progress. miR-140 overexpression also improved the anti-viability effects of doxorubicin, suggesting its potential in reducing the drug resistance of gastric cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (mainland).

ABSTRACT
BACKGROUND Gastric cancer is a malignant tumor with a high morbidity and mortality. MicroRNAs are important regulators of gene expression, influencing the progression of gastric cancer. This study aimed to reveal the role of microRNA-140 (miR-140) in gastric cancer cell proliferation and its potential mechanisms. MATERIAL AND METHODS Gastric cancer tissues and cell lines BGC-823, SGC-7901, and HGC-27 were used to analyze miR-140 levels compared to normal tissues and cell line GES-1. In HGC-27 cells transfected with miR-140 mimic, we performed MTT, colony formation assay, and cell cycle assay by flow cytometry. SOX4, a predicted target of miR-140, was mutated to verify its regulation by miR-140, and was overexpressed to analyze its function in cell proliferation. Doxorubicin treatment was performed to investigate the effect of miR-140 on drug resistance. RESULTS miR-140 was down-regulated in gastric cancer tissues and cell lines, with the lowest expression level in HGC-27. miR-140 overexpression inhibited HGC-27 cell viability and colony formation and resulted in G0/G1 arrest. miR-140 suppressed SOX4 expression via binding to the 3' untranslated region, while the mutant SOX4 could not be regulated. Overexpressing SOX4 led to promoted cell viability, colony formation, and cell cycle progress. miR-140 overexpression also improved the anti-viability effects of doxorubicin, suggesting its potential in reducing the drug resistance of gastric cells. CONCLUSIONS These findings suggest that miR-140 directly inhibits SOX4, which might be one of its mechanisms in suppressing gastric cancer cell proliferation. This study provides a promising therapeutic strategy for treating gastric cancer and facilitates microRNA research in various diseases.

No MeSH data available.


Related in: MedlinePlus