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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 is down-regulated in gastric cancer and inhibits cell proliferation. (A) miR-140 is down-regulated in gastric cancer tissues compared to normal tissues. (B) miR-140 is down-regulated in gastric cancer cell lines, including HGC-27, BGC-823, and SGC-7901, compared to normal gastric cell line GES-1. (C) MTT results indicate that HGC-27 cells transfected with miR-140 mimic possess lower viability than mimic control. Significant differences are found at 48 and 72 h after transfection. (D) Colony formation experiment shows the HGC-27 cells transfected with miR-140 mimic possess lower colony formation efficiency after 2 weeks of incubation. * P<0.05; *** P<0.001.
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f1-medscimonit-22-2243: miR-140 is down-regulated in gastric cancer and inhibits cell proliferation. (A) miR-140 is down-regulated in gastric cancer tissues compared to normal tissues. (B) miR-140 is down-regulated in gastric cancer cell lines, including HGC-27, BGC-823, and SGC-7901, compared to normal gastric cell line GES-1. (C) MTT results indicate that HGC-27 cells transfected with miR-140 mimic possess lower viability than mimic control. Significant differences are found at 48 and 72 h after transfection. (D) Colony formation experiment shows the HGC-27 cells transfected with miR-140 mimic possess lower colony formation efficiency after 2 weeks of incubation. * P<0.05; *** P<0.001.

Mentions: The miR-140 level in tissue samples was detected by qPCR, and results indicated a significant down-regulation of miR-140 in gastric cancer tissues compared to normal tissues (P<0.001, Figure 1A), which led us to suspect the role of miR-140 in modulating gastric cancer cells. The miR-140 level was also detected in the normal gastric cells GES-1, as well as in gastric cancer cells, including HGC-27 (undifferentiated), BGC-823 (lightly differentiated), and SGC-7901 (moderately differentiated), which differed in their degree of cellular differentiation (Figure 1B). We found that the miR-140 expression was down-regulated in all of the detected gastric cancer cells (P<0.05), and the HGC-27 cells possessed the lowest miR-140 expression (P<0.001), in line with its undifferentiated feature. It was likely that the gastric cells with a lower differentiation degree exhibited more significant differences from normal cells, which would be more suitable to use in studying miR-140 functions. Therefore, the following experiments were performed in the HGC-27 cells.


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 is down-regulated in gastric cancer and inhibits cell proliferation. (A) miR-140 is down-regulated in gastric cancer tissues compared to normal tissues. (B) miR-140 is down-regulated in gastric cancer cell lines, including HGC-27, BGC-823, and SGC-7901, compared to normal gastric cell line GES-1. (C) MTT results indicate that HGC-27 cells transfected with miR-140 mimic possess lower viability than mimic control. Significant differences are found at 48 and 72 h after transfection. (D) Colony formation experiment shows the HGC-27 cells transfected with miR-140 mimic possess lower colony formation efficiency after 2 weeks of incubation. * P<0.05; *** P<0.001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4930272&req=5

f1-medscimonit-22-2243: miR-140 is down-regulated in gastric cancer and inhibits cell proliferation. (A) miR-140 is down-regulated in gastric cancer tissues compared to normal tissues. (B) miR-140 is down-regulated in gastric cancer cell lines, including HGC-27, BGC-823, and SGC-7901, compared to normal gastric cell line GES-1. (C) MTT results indicate that HGC-27 cells transfected with miR-140 mimic possess lower viability than mimic control. Significant differences are found at 48 and 72 h after transfection. (D) Colony formation experiment shows the HGC-27 cells transfected with miR-140 mimic possess lower colony formation efficiency after 2 weeks of incubation. * P<0.05; *** P<0.001.
Mentions: The miR-140 level in tissue samples was detected by qPCR, and results indicated a significant down-regulation of miR-140 in gastric cancer tissues compared to normal tissues (P<0.001, Figure 1A), which led us to suspect the role of miR-140 in modulating gastric cancer cells. The miR-140 level was also detected in the normal gastric cells GES-1, as well as in gastric cancer cells, including HGC-27 (undifferentiated), BGC-823 (lightly differentiated), and SGC-7901 (moderately differentiated), which differed in their degree of cellular differentiation (Figure 1B). We found that the miR-140 expression was down-regulated in all of the detected gastric cancer cells (P<0.05), and the HGC-27 cells possessed the lowest miR-140 expression (P<0.001), in line with its undifferentiated feature. It was likely that the gastric cells with a lower differentiation degree exhibited more significant differences from normal cells, which would be more suitable to use in studying miR-140 functions. Therefore, the following experiments were performed in the HGC-27 cells.

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