Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma

Li, Binkui; He, Liru; Zuo, Dinglan; He, Wei; Wang, Yongjin; Zhang, Yuanping; Liu, Wenwu; Yuan, Yunfei

doi:10.7150/jca.17496

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J Cancer 2017; 8(6):940-949. doi:10.7150/jca.17496 This issue Cite

Research Paper

Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma

Binkui Li^1,3,4✉, Liru He^2,3,4, Dinglan Zuo^3,4, Wei He^1,3,4, Yongjin Wang^1,3,4, Yuanping Zhang^1,3,4, Wenwu Liu^1,3,4, Yunfei Yuan^1,3,4✉

1. Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China;
2. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;
3. State Key Laboratory of Oncology in South China, Guangzhou, China;
4. Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Citation:

Li B, He L, Zuo D, He W, Wang Y, Zhang Y, Liu W, Yuan Y. Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma. J Cancer 2017; 8(6):940-949. doi:10.7150/jca.17496. https://www.jcancer.org/v08p0940.htm

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Abstract

The Warburg effect is one of the major metabolic changes of cancer cells, which characterized by high level of glycolysis even in the presence of oxygen. However, the role of microRNAs (miRNAs) in regulating the glycolytic switch in cancer cells has not been well explored. In this study, we demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in hepatocellular carcinoma (HCC). MiR-199a-5p directly targets the 3′-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells. Moreover, under hypoxic conditions, the expression of miR-199a-5p is suppressed by the up-regulation of HIF-1α. Thus, mutual regulation between miR-199a-5p and HIF-1α forms a positive feedback loop to promote glycolysis in HCC cells. Furthermore, miR-199a-5p is down-regulated in human HCC tissues and its low-level expression is associated with a worse survival of patients with HCC. Our findings suggest that miR-199a-5p/HIF-1α axis is critical in the regulation of the Warburg effect and also implicate miR-199a-5p as a potential therapeutic target for HCC.

Keywords: miR-199a-5p, the Warburg effect, hypoxia, HIF-1α, hepatocellular carcinoma.

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APA

Li, B., He, L., Zuo, D., He, W., Wang, Y., Zhang, Y., Liu, W., Yuan, Y. (2017). Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma. Journal of Cancer, 8(6), 940-949. https://doi.org/10.7150/jca.17496.

ACS

Li, B.; He, L.; Zuo, D.; He, W.; Wang, Y.; Zhang, Y.; Liu, W.; Yuan, Y. Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma. J. Cancer 2017, 8 (6), 940-949. DOI: 10.7150/jca.17496.

NLM

CSE

Li B, He L, Zuo D, He W, Wang Y, Zhang Y, Liu W, Yuan Y. 2017. Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma. J Cancer. 8(6):940-949.

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