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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 apoptosis in mouse breast tunmor model.(A) Quantitative analysis of miR-497 expression in tumor tissues by qRT-PCR analysis; (B–D) Proteins expression of VEGFR2, Bcl-2, and Bax. Data were expressed as mean ± EM, n = 3; **P < 0.01 vs. control group. (E) Cell apoptosis was determined by TUNEL assay and shown as percentage. (F) Representative apoptotic images of each group were taken at a magnification of ×200. Data were expressed as mean ± SEM, n = 10; **P < 0.01 vs. control group.
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f4: Effects of miR-497 overexpression on apoptosis in mouse breast tunmor model.(A) Quantitative analysis of miR-497 expression in tumor tissues by qRT-PCR analysis; (B–D) Proteins expression of VEGFR2, Bcl-2, and Bax. Data were expressed as mean ± EM, n = 3; **P < 0.01 vs. control group. (E) Cell apoptosis was determined by TUNEL assay and shown as percentage. (F) Representative apoptotic images of each group were taken at a magnification of ×200. Data were expressed as mean ± SEM, n = 10; **P < 0.01 vs. control group.

Mentions: The mice were sacrificed and tumor tissues were removed after in vivo bioluminescent imaging on 14 d. The miR-497 expression level of tumor tissues was confirmed by real-time PCR assay. Compared with the control, the expression level of miR-497 significantly increased in miR-497 mimic group (P < 0.05) (Fig. 4A). To evaluate the pro-apoptosis role of miR-497 via targeting VEGFR2 and its downstream proteins in vivo, western blotting was performed to detect the expression of VEGFR2, Bax and Bcl-2. The data showed that compared with control, VEGFR2 and Bcl-2 expression in miR-497 mimic group was significant lower, while pro-apoptosis protein Bax was higher (P < 0.05) (Fig. 4B–D).


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 apoptosis in mouse breast tunmor model.(A) Quantitative analysis of miR-497 expression in tumor tissues by qRT-PCR analysis; (B–D) Proteins expression of VEGFR2, Bcl-2, and Bax. Data were expressed as mean ± EM, n = 3; **P < 0.01 vs. control group. (E) Cell apoptosis was determined by TUNEL assay and shown as percentage. (F) Representative apoptotic images of each group were taken at a magnification of ×200. Data were expressed as mean ± SEM, n = 10; **P < 0.01 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Effects of miR-497 overexpression on apoptosis in mouse breast tunmor model.(A) Quantitative analysis of miR-497 expression in tumor tissues by qRT-PCR analysis; (B–D) Proteins expression of VEGFR2, Bcl-2, and Bax. Data were expressed as mean ± EM, n = 3; **P < 0.01 vs. control group. (E) Cell apoptosis was determined by TUNEL assay and shown as percentage. (F) Representative apoptotic images of each group were taken at a magnification of ×200. Data were expressed as mean ± SEM, n = 10; **P < 0.01 vs. control group.
Mentions: The mice were sacrificed and tumor tissues were removed after in vivo bioluminescent imaging on 14 d. The miR-497 expression level of tumor tissues was confirmed by real-time PCR assay. Compared with the control, the expression level of miR-497 significantly increased in miR-497 mimic group (P < 0.05) (Fig. 4A). To evaluate the pro-apoptosis role of miR-497 via targeting VEGFR2 and its downstream proteins in vivo, western blotting was performed to detect the expression of VEGFR2, Bax and Bcl-2. The data showed that compared with control, VEGFR2 and Bcl-2 expression in miR-497 mimic group was significant lower, while pro-apoptosis protein Bax was higher (P < 0.05) (Fig. 4B–D).

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