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Hypoxia-inducible MiR-182 promotes angiogenesis by targeting RASA1 in hepatocellular carcinoma.

Du C, Weng X, Hu W, Lv Z, Xiao H, Ding C, Gyabaah OA, Xie H, Zhou L, Wu J, Zheng S - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: We found that miR-182 was upregulated in the hypoxia-based microarray.We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues.In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

ABSTRACT

Background: Hypoxia is a common feature of solid tumors, including HCC. And hypoxia has been reported to play an important role in HCC progression. However, the potential mechanism of miRNAs in hypoxia mediating HCC progression still remains unclear.

Methods: The HCC cells were cultured in the atmosphere of 1 % oxygen to induce hypoxia. The microRNA microarray was employed to search for the hypoxia-inducible miRNAs. RT-PCR, western blot and immunohistochemistry were used to detect the RNA and protein levels. HUVEC were applied to explore the angiogenesis level.

Results: We found that miR-182 was upregulated in the hypoxia-based microarray. We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues. In vitro capilliary tube formation assays showed that the miR-182 promoted angiogenesis. RASA1 was demonstrated as the direct target of miR-182. In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182. Besides, RASA1 was also decreased in the hypoxia HCC cells while the inhibition of miR-182 partially restored the level of RASA1.

Conclusions: Our data showed that hypoxia regulated the expression of miR-182 and RASA1 to promote HCC angiogenesis.

No MeSH data available.


Related in: MedlinePlus

The level of miR-182 was increased in HCC tissues and promotes angiogenesis. a The level of MiR-182 was examined by RT-PCR in 36 pairs of HCC tissues and their corresponding normal tissues. b The percent of up-regulation of miR-182 in HCC was shown. c Capillary tube formation assays of HUVECs were performed by using 75 % TCM derived from SK-HEP-1 and HCC-LM3 cells treated with miR-182 mimics or NC or anti-miR-182. The relative images were shown at the 100× magnification and the results are representative of three independent experiments. (*P < 0.05, **P < 0.01)
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Fig2: The level of miR-182 was increased in HCC tissues and promotes angiogenesis. a The level of MiR-182 was examined by RT-PCR in 36 pairs of HCC tissues and their corresponding normal tissues. b The percent of up-regulation of miR-182 in HCC was shown. c Capillary tube formation assays of HUVECs were performed by using 75 % TCM derived from SK-HEP-1 and HCC-LM3 cells treated with miR-182 mimics or NC or anti-miR-182. The relative images were shown at the 100× magnification and the results are representative of three independent experiments. (*P < 0.05, **P < 0.01)

Mentions: We then explored the expression of miR-182 in 36 pairs of HCC tissues. Consistent with a previous study [14], the level of miR-182 was significantly increased in HCC tumor tissues compared to the corresponding normal tissues (Fig. 2a, b). We then examined the clinicopathologic significance of miR-182 in HCC by choosing the median of miR-182 as the cut-off point to separate the low-miR-182 group and the high-miR-182 group (Table 2). We found that the upregulation of miR-182 was more frequently observed in the patients with big tumor size (P = 0.018) and portal vein invasion (P = 0.027). However no significant correlation was found between miR-182 and other clinicopathologic data, including age, gender tumor number, TNM staging, grade and AFP level.Fig. 2


Hypoxia-inducible MiR-182 promotes angiogenesis by targeting RASA1 in hepatocellular carcinoma.

Du C, Weng X, Hu W, Lv Z, Xiao H, Ding C, Gyabaah OA, Xie H, Zhou L, Wu J, Zheng S - J. Exp. Clin. Cancer Res. (2015)

The level of miR-182 was increased in HCC tissues and promotes angiogenesis. a The level of MiR-182 was examined by RT-PCR in 36 pairs of HCC tissues and their corresponding normal tissues. b The percent of up-regulation of miR-182 in HCC was shown. c Capillary tube formation assays of HUVECs were performed by using 75 % TCM derived from SK-HEP-1 and HCC-LM3 cells treated with miR-182 mimics or NC or anti-miR-182. The relative images were shown at the 100× magnification and the results are representative of three independent experiments. (*P < 0.05, **P < 0.01)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493986&req=5

Fig2: The level of miR-182 was increased in HCC tissues and promotes angiogenesis. a The level of MiR-182 was examined by RT-PCR in 36 pairs of HCC tissues and their corresponding normal tissues. b The percent of up-regulation of miR-182 in HCC was shown. c Capillary tube formation assays of HUVECs were performed by using 75 % TCM derived from SK-HEP-1 and HCC-LM3 cells treated with miR-182 mimics or NC or anti-miR-182. The relative images were shown at the 100× magnification and the results are representative of three independent experiments. (*P < 0.05, **P < 0.01)
Mentions: We then explored the expression of miR-182 in 36 pairs of HCC tissues. Consistent with a previous study [14], the level of miR-182 was significantly increased in HCC tumor tissues compared to the corresponding normal tissues (Fig. 2a, b). We then examined the clinicopathologic significance of miR-182 in HCC by choosing the median of miR-182 as the cut-off point to separate the low-miR-182 group and the high-miR-182 group (Table 2). We found that the upregulation of miR-182 was more frequently observed in the patients with big tumor size (P = 0.018) and portal vein invasion (P = 0.027). However no significant correlation was found between miR-182 and other clinicopathologic data, including age, gender tumor number, TNM staging, grade and AFP level.Fig. 2

Bottom Line: We found that miR-182 was upregulated in the hypoxia-based microarray.We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues.In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

ABSTRACT

Background: Hypoxia is a common feature of solid tumors, including HCC. And hypoxia has been reported to play an important role in HCC progression. However, the potential mechanism of miRNAs in hypoxia mediating HCC progression still remains unclear.

Methods: The HCC cells were cultured in the atmosphere of 1 % oxygen to induce hypoxia. The microRNA microarray was employed to search for the hypoxia-inducible miRNAs. RT-PCR, western blot and immunohistochemistry were used to detect the RNA and protein levels. HUVEC were applied to explore the angiogenesis level.

Results: We found that miR-182 was upregulated in the hypoxia-based microarray. We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues. In vitro capilliary tube formation assays showed that the miR-182 promoted angiogenesis. RASA1 was demonstrated as the direct target of miR-182. In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182. Besides, RASA1 was also decreased in the hypoxia HCC cells while the inhibition of miR-182 partially restored the level of RASA1.

Conclusions: Our data showed that hypoxia regulated the expression of miR-182 and RASA1 to promote HCC angiogenesis.

No MeSH data available.


Related in: MedlinePlus