Limits...
Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2.

Tu Y, Liu L, Zhao D, Liu Y, Ma X, Fan Y, Wan L, Huang T, Cheng Z, Shen B - Sci Rep (2015)

Bottom Line: The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo.Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway.Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.

ABSTRACT
Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.

No MeSH data available.


Related in: MedlinePlus

Effects of miR-497 overexpression on Raf/MEK/ERK signaling pathway in mouse breast tumor model.Proteins expression of Raf, Total-MEK, p-MEK, Total-ERK and p-ERK were determined by western blotting assay. Data were expressed as mean ± SEM, n = 3; **P < 0.01 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4561885&req=5

f6: Effects of miR-497 overexpression on Raf/MEK/ERK signaling pathway in mouse breast tumor model.Proteins expression of Raf, Total-MEK, p-MEK, Total-ERK and p-ERK were determined by western blotting assay. Data were expressed as mean ± SEM, n = 3; **P < 0.01 vs. control group.

Mentions: Next, in order to elucidate the anti-angiogenesis effects of miR-497 mediated by down-regulation of VEGFR2/Raf/ERK/MEK pathway in breast tumor, we investigated the expression of angiogenesis-related signal pathway proteins in tumor lysates from these three groups. Western blotting analysis displayed that overexpression of miR-497 could down-regulate the endogenous levels of Raf, p-ERK and p-MEK in vivo (P > 0.05) (Fig. 6), meanwhile the expression of total ERK and MEK did not change compared to control (P > 0.05) (Fig. 6). The above results confirmed that miR-497 could markedly inhibit breast tumor angiogenesis in vivo.


Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2.

Tu Y, Liu L, Zhao D, Liu Y, Ma X, Fan Y, Wan L, Huang T, Cheng Z, Shen B - Sci Rep (2015)

Effects of miR-497 overexpression on Raf/MEK/ERK signaling pathway in mouse breast tumor model.Proteins expression of Raf, Total-MEK, p-MEK, Total-ERK and p-ERK were determined by western blotting assay. Data were expressed as mean ± SEM, n = 3; **P < 0.01 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561885&req=5

f6: Effects of miR-497 overexpression on Raf/MEK/ERK signaling pathway in mouse breast tumor model.Proteins expression of Raf, Total-MEK, p-MEK, Total-ERK and p-ERK were determined by western blotting assay. Data were expressed as mean ± SEM, n = 3; **P < 0.01 vs. control group.
Mentions: Next, in order to elucidate the anti-angiogenesis effects of miR-497 mediated by down-regulation of VEGFR2/Raf/ERK/MEK pathway in breast tumor, we investigated the expression of angiogenesis-related signal pathway proteins in tumor lysates from these three groups. Western blotting analysis displayed that overexpression of miR-497 could down-regulate the endogenous levels of Raf, p-ERK and p-MEK in vivo (P > 0.05) (Fig. 6), meanwhile the expression of total ERK and MEK did not change compared to control (P > 0.05) (Fig. 6). The above results confirmed that miR-497 could markedly inhibit breast tumor angiogenesis in vivo.

Bottom Line: The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo.Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway.Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.

ABSTRACT
Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.

No MeSH data available.


Related in: MedlinePlus