Theranostics 2020; 10(12):5209-5224. doi:10.7150/thno.43640 This issue Cite

Research Paper

Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma

Yadi Liao1*, Chenwei Wang1,2*, Zhiwen Yang1,2, Wenwu Liu1, Yichuan Yuan1,2, Kai Li1,2, Yuanping Zhang1,2, Yongjin Wang1,2, Yunxing Shi1,2, Yuxiong Qiu1,2, Dinglan Zuo1, Wei He1,2, Jiliang Qiu1,2, Xinyuan Guan1,3, Yunfei Yuan1,2✉, Binkui Li1,2✉

1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
2. Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China
3. Department of Clinical Oncology, The University of Hong Kong, 852 Hong Kong, P. R. China
*Yadi Liao and Chenwei Wang contributed equally to this work.

Citation:
Liao Y, Wang C, Yang Z, Liu W, Yuan Y, Li K, Zhang Y, Wang Y, Shi Y, Qiu Y, Zuo D, He W, Qiu J, Guan X, Yuan Y, Li B. Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma. Theranostics 2020; 10(12):5209-5224. doi:10.7150/thno.43640. https://www.thno.org/v10p5209.htm
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Abstract

Graphic abstract

Angiogenesis, one of the hallmarks of cancer, is essential for both tumor growth and metastasis. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are largely unknown. Here, we report the role of HOXA5 in tumor angiogenesis of HCC.

Methods: The expression of miR-130b-3p and HOXA5 was determined by qRT-PCR and immunohistochemistry, respectively. Capillary tube formation assay, chicken chorioallantoic membrane assay, and subcutaneous xenograft experiments were performed to investigate the role of miR-130-3p and HOXA5. Luciferase reporter assay and chromatin immunoprecipitation assay were performed to evaluate the interaction between Sp1, miR-130b-3p and HOXA5.

Results: miR-130b-3p was found up-regulated in HCC and correlated with a poor prognosis. miR-130b-3p promoted HCC angiogenesis both in vitro and in vivo. Mechanistically, HOXA5 was validated as a direct target of miR-130b-3p. Furthermore, we demonstrated that HOXA5 was down-regulated in HCC and its down-regulation was associated with larger tumor size, shorter overall survival, and higher recurrence probability. Moreover, HOXA5 was significantly associated with angiogenesis biomarkers such as CD31 and CD34. Functional studies revealed that the knockdown of HOXA5 also significantly promoted HCC angiogenesis both in vitro and in vivo. Knocking-down HOXA5 significantly provoked HCC cells to induce the capillary tube formation, migration and proliferation of endothelial cells. In xenograft animal models, we found that a decrease of HOXA5 effectively enhanced tumor growth and increased microvessel densities. We further demonstrated that miR-130b-3p could be directly transcriptionally regulated by Sp1.

Conclusions: This study showed that a dysregulation in the Sp1/miR-130b-3p/HOXA5 axis contributed to HCC progression and angiogenesis, and that HOXA5 can be considered as a promising therapeutic target for treating HCC.

Keywords: Hepatocellular carcinoma, Angiogenesis, miR-130b-3p, HOXA5


Citation styles

APA
Liao, Y., Wang, C., Yang, Z., Liu, W., Yuan, Y., Li, K., Zhang, Y., Wang, Y., Shi, Y., Qiu, Y., Zuo, D., He, W., Qiu, J., Guan, X., Yuan, Y., Li, B. (2020). Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma. Theranostics, 10(12), 5209-5224. https://doi.org/10.7150/thno.43640.

ACS
Liao, Y.; Wang, C.; Yang, Z.; Liu, W.; Yuan, Y.; Li, K.; Zhang, Y.; Wang, Y.; Shi, Y.; Qiu, Y.; Zuo, D.; He, W.; Qiu, J.; Guan, X.; Yuan, Y.; Li, B. Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma. Theranostics 2020, 10 (12), 5209-5224. DOI: 10.7150/thno.43640.

NLM
Liao Y, Wang C, Yang Z, Liu W, Yuan Y, Li K, Zhang Y, Wang Y, Shi Y, Qiu Y, Zuo D, He W, Qiu J, Guan X, Yuan Y, Li B. Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma. Theranostics 2020; 10(12):5209-5224. doi:10.7150/thno.43640. https://www.thno.org/v10p5209.htm

CSE
Liao Y, Wang C, Yang Z, Liu W, Yuan Y, Li K, Zhang Y, Wang Y, Shi Y, Qiu Y, Zuo D, He W, Qiu J, Guan X, Yuan Y, Li B. 2020. Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma. Theranostics. 10(12):5209-5224.

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