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MicroRNA-519a promotes proliferation and inhibits apoptosis of hepatocellular carcinoma cells by targeting FOXF2.

Shao J, Cao J, Liu Y, Mei H, Zhang Y, Xu W - FEBS Open Bio (2015)

Bottom Line: Importantly, up-regulation of miR-519a reduced the expression of FOXF2 mRNA and protein in Huh7 cells, while down-regulation of miR-519a resulted in increased expression of FOXF2 in SMMC-7721 cells.Mechanistically, the effects of miR-519a knockdown on SMMC-7721 cells were abrogated by FOXF2 repression.In conclusion, miR-519a is a novel prognostic predictor for HCC patients and it may potentiate proliferation and inhibits apoptosis of HCC cells by targeting FOXF2.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.

ABSTRACT
Recent studies report that microRNA-519a (miR-519a) is a novel oncomir, which facilitates the onset and progression of human cancers. However, the clinical significance of miR-519a and its functional role and underlying mechanisms in hepatocellular carcinoma (HCC) are poorly investigated. In the present study, elevated expression of miR-519a was observed in HCC tissues compared with adjacent non-tumor tissues. The increased level of miR-519a expression was significantly correlated with adverse clinical features of HCC including hepatitis B virus (HBV) infection, large tumor size, cirrhosis and advanced tumor-node-metastasis tumor stage. Furthermore, high expression of miR-519a was prominently associated with a poorer 5-year overall survival and recurrence-free survival of HCC patients. Gain- and loss-of function experiments showed that miR-519a overexpression enhanced proliferation and reduced apoptosis of Huh7 cells. By contrast, miR-519a knockdown inhibited SMMC-7721 cell proliferation and induced apoptosis. Importantly, up-regulation of miR-519a reduced the expression of FOXF2 mRNA and protein in Huh7 cells, while down-regulation of miR-519a resulted in increased expression of FOXF2 in SMMC-7721 cells. An inverse correlation between mRNA levels of miR-519a and FOXF2 was observed in HCC tissues. Thus, Forkhead box F2 (FOXF2) was identified as a downstream target of miR-519a in HCC. Mechanistically, the effects of miR-519a knockdown on SMMC-7721 cells were abrogated by FOXF2 repression. In conclusion, miR-519a is a novel prognostic predictor for HCC patients and it may potentiate proliferation and inhibits apoptosis of HCC cells by targeting FOXF2.

No MeSH data available.


Related in: MedlinePlus

Overexpression of miR-519a enhanced proliferation and reduced apoptosis of Huh7 cells. (A) Transfection of miR-519a mimics significantly increased the expression level of miR-519a in Huh7 cells. n = three independent experiments, ∗P < 0.05. (B) Cell proliferation as measured by BrdU incorporation assays was increased after miR-519a overexpression in Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05. (C) Overexpression of miR-519a significantly decreased the percentage of apoptotic Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05.
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f0010: Overexpression of miR-519a enhanced proliferation and reduced apoptosis of Huh7 cells. (A) Transfection of miR-519a mimics significantly increased the expression level of miR-519a in Huh7 cells. n = three independent experiments, ∗P < 0.05. (B) Cell proliferation as measured by BrdU incorporation assays was increased after miR-519a overexpression in Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05. (C) Overexpression of miR-519a significantly decreased the percentage of apoptotic Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05.

Mentions: To elucidate the functional role of miR-519a in HCC, we further examined the proliferation and apoptosis of HCC cells after miR-519a alteration through gain- and loss-of-function assays. Huh7 cells that were transfected with miR-519a mimics showed a significant up-regulation of miR-519a expression compared to control cells (P < 0.05, Fig. 2A). Then, we performed BrdU incorporation assays and found that miR-519a overexpression in Huh7 cells resulted in significant increased proliferative ability (P < 0.05, Fig. 2B). At the same time, decreased apoptosis of Huh7 cells were observed after miR-519a overexpression (P < 0.05, Fig. 2C). On the other hand, SMMC-7721 cells that were transfected with miR-519a inhibitors led to an obvious down-regulation of miR-519a expression (P < 0.05, Fig. 3A). And down-regulation of miR-519a significantly inhibited cell proliferation (P < 0.05, Fig. 3B) and induced apoptosis (P < 0.05, Fig. 3C) in SMMC-7721 cells. These results indicate that miR-519a can potentiate proliferation and inhibit apoptosis of HCC cells in vitro.


MicroRNA-519a promotes proliferation and inhibits apoptosis of hepatocellular carcinoma cells by targeting FOXF2.

Shao J, Cao J, Liu Y, Mei H, Zhang Y, Xu W - FEBS Open Bio (2015)

Overexpression of miR-519a enhanced proliferation and reduced apoptosis of Huh7 cells. (A) Transfection of miR-519a mimics significantly increased the expression level of miR-519a in Huh7 cells. n = three independent experiments, ∗P < 0.05. (B) Cell proliferation as measured by BrdU incorporation assays was increased after miR-519a overexpression in Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05. (C) Overexpression of miR-519a significantly decreased the percentage of apoptotic Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4660191&req=5

f0010: Overexpression of miR-519a enhanced proliferation and reduced apoptosis of Huh7 cells. (A) Transfection of miR-519a mimics significantly increased the expression level of miR-519a in Huh7 cells. n = three independent experiments, ∗P < 0.05. (B) Cell proliferation as measured by BrdU incorporation assays was increased after miR-519a overexpression in Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05. (C) Overexpression of miR-519a significantly decreased the percentage of apoptotic Huh7 cells. n = 3 repeats with similar results, ∗P < 0.05.
Mentions: To elucidate the functional role of miR-519a in HCC, we further examined the proliferation and apoptosis of HCC cells after miR-519a alteration through gain- and loss-of-function assays. Huh7 cells that were transfected with miR-519a mimics showed a significant up-regulation of miR-519a expression compared to control cells (P < 0.05, Fig. 2A). Then, we performed BrdU incorporation assays and found that miR-519a overexpression in Huh7 cells resulted in significant increased proliferative ability (P < 0.05, Fig. 2B). At the same time, decreased apoptosis of Huh7 cells were observed after miR-519a overexpression (P < 0.05, Fig. 2C). On the other hand, SMMC-7721 cells that were transfected with miR-519a inhibitors led to an obvious down-regulation of miR-519a expression (P < 0.05, Fig. 3A). And down-regulation of miR-519a significantly inhibited cell proliferation (P < 0.05, Fig. 3B) and induced apoptosis (P < 0.05, Fig. 3C) in SMMC-7721 cells. These results indicate that miR-519a can potentiate proliferation and inhibit apoptosis of HCC cells in vitro.

Bottom Line: Importantly, up-regulation of miR-519a reduced the expression of FOXF2 mRNA and protein in Huh7 cells, while down-regulation of miR-519a resulted in increased expression of FOXF2 in SMMC-7721 cells.Mechanistically, the effects of miR-519a knockdown on SMMC-7721 cells were abrogated by FOXF2 repression.In conclusion, miR-519a is a novel prognostic predictor for HCC patients and it may potentiate proliferation and inhibits apoptosis of HCC cells by targeting FOXF2.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.

ABSTRACT
Recent studies report that microRNA-519a (miR-519a) is a novel oncomir, which facilitates the onset and progression of human cancers. However, the clinical significance of miR-519a and its functional role and underlying mechanisms in hepatocellular carcinoma (HCC) are poorly investigated. In the present study, elevated expression of miR-519a was observed in HCC tissues compared with adjacent non-tumor tissues. The increased level of miR-519a expression was significantly correlated with adverse clinical features of HCC including hepatitis B virus (HBV) infection, large tumor size, cirrhosis and advanced tumor-node-metastasis tumor stage. Furthermore, high expression of miR-519a was prominently associated with a poorer 5-year overall survival and recurrence-free survival of HCC patients. Gain- and loss-of function experiments showed that miR-519a overexpression enhanced proliferation and reduced apoptosis of Huh7 cells. By contrast, miR-519a knockdown inhibited SMMC-7721 cell proliferation and induced apoptosis. Importantly, up-regulation of miR-519a reduced the expression of FOXF2 mRNA and protein in Huh7 cells, while down-regulation of miR-519a resulted in increased expression of FOXF2 in SMMC-7721 cells. An inverse correlation between mRNA levels of miR-519a and FOXF2 was observed in HCC tissues. Thus, Forkhead box F2 (FOXF2) was identified as a downstream target of miR-519a in HCC. Mechanistically, the effects of miR-519a knockdown on SMMC-7721 cells were abrogated by FOXF2 repression. In conclusion, miR-519a is a novel prognostic predictor for HCC patients and it may potentiate proliferation and inhibits apoptosis of HCC cells by targeting FOXF2.

No MeSH data available.


Related in: MedlinePlus