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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

FOXF2 knockdown rescue the effects of miR-519a repression on SMCC-7721 cells. (A) miR-519a down-regulating SMMC-7721 cells that were transfected with scrambled siRNA or FOXF2 siRNA were subjected to immunoblotting for FOXF2. n = 3 repeats with similar results; ∗P < 0.05. (B) BrdU incorporation assays indicated that FOXF2 knockdown prominently increased cell proliferation in miR-519a down-regulating SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05. (C) FOXF2 knockdown significantly rescued miR-519a down-regulating-induced apoptosis of SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05.
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f0030: FOXF2 knockdown rescue the effects of miR-519a repression on SMCC-7721 cells. (A) miR-519a down-regulating SMMC-7721 cells that were transfected with scrambled siRNA or FOXF2 siRNA were subjected to immunoblotting for FOXF2. n = 3 repeats with similar results; ∗P < 0.05. (B) BrdU incorporation assays indicated that FOXF2 knockdown prominently increased cell proliferation in miR-519a down-regulating SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05. (C) FOXF2 knockdown significantly rescued miR-519a down-regulating-induced apoptosis of SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05.

Mentions: To further confirm that FOXF2 is a functional target of miR-519a, a specific FOXF2 siRNA was transfected into miR-519a down-regulating SMMC-7721 cells. FOXF2 knockdown was confirmed by Western blot analysis (P < 0.05, Fig. 6A). Furthermore, we found that cell proliferation was remarkably increased after FOXF2 knockdown in miR-519a down-regulating SMMC-7721 cells (P < 0.05, Fig. 6B). Moreover, FOXF2 knockdown significantly rescued down-regulation of miR-519a-induced apoptosis of SMMC-7721 cells (P < 0.05, Fig. 6C). Thus, these results provide further evidence supporting FOXF2 as a downstream mediator of miR-519a.


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)

FOXF2 knockdown rescue the effects of miR-519a repression on SMCC-7721 cells. (A) miR-519a down-regulating SMMC-7721 cells that were transfected with scrambled siRNA or FOXF2 siRNA were subjected to immunoblotting for FOXF2. n = 3 repeats with similar results; ∗P < 0.05. (B) BrdU incorporation assays indicated that FOXF2 knockdown prominently increased cell proliferation in miR-519a down-regulating SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05. (C) FOXF2 knockdown significantly rescued miR-519a down-regulating-induced apoptosis of SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05.
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Related In: Results  -  Collection

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f0030: FOXF2 knockdown rescue the effects of miR-519a repression on SMCC-7721 cells. (A) miR-519a down-regulating SMMC-7721 cells that were transfected with scrambled siRNA or FOXF2 siRNA were subjected to immunoblotting for FOXF2. n = 3 repeats with similar results; ∗P < 0.05. (B) BrdU incorporation assays indicated that FOXF2 knockdown prominently increased cell proliferation in miR-519a down-regulating SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05. (C) FOXF2 knockdown significantly rescued miR-519a down-regulating-induced apoptosis of SMMC-7721 cells. n = 3 repeats with similar results; ∗P < 0.05.
Mentions: To further confirm that FOXF2 is a functional target of miR-519a, a specific FOXF2 siRNA was transfected into miR-519a down-regulating SMMC-7721 cells. FOXF2 knockdown was confirmed by Western blot analysis (P < 0.05, Fig. 6A). Furthermore, we found that cell proliferation was remarkably increased after FOXF2 knockdown in miR-519a down-regulating SMMC-7721 cells (P < 0.05, Fig. 6B). Moreover, FOXF2 knockdown significantly rescued down-regulation of miR-519a-induced apoptosis of SMMC-7721 cells (P < 0.05, Fig. 6C). Thus, these results provide further evidence supporting FOXF2 as a downstream mediator of miR-519a.

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