c-Myc modulates glucose metabolism via regulation of miR-184/PKM2 pathway in clear-cell renal cell carcinoma

Huang,Jiwei; Kong,Wen; Zhang,Jin; Chen,Yonghui; Xue,Wei; Liu,Dongming; Huang,Yiran

doi:10.3892/ijo.2016.3622

c-Myc modulates glucose metabolism via regulation of miR-184/PKM2 pathway in clear-cell renal cell carcinoma

Authors:
- Jiwei Huang
- Wen Kong
- Jin Zhang
- Yonghui Chen
- Wei Xue
- Dongming Liu
- Yiran Huang
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Affiliations: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
Published online on: July 14, 2016 https://doi.org/10.3892/ijo.2016.3622
Pages: 1569-1575

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Abstract

Renal cell carcinoma (RCC) is one of the most malignant tumors worldwide. Among all subtypes of RCC, clear-cell RCC (ccRCC) is the most common and aggressive one. The difficulty in overcoming resistance of traditional treatment is a threat for ccRCC therapies. Therefore, to understand the mechanism that underlies ccRCC progression is critical for new drug development. In the present study, we identified that miR-184 could be downregulated by c-Myc, which is different from the standard opinion that c-Myc is a target of miR-184. Overexpression of pre-miR-184 changed the metabolic and proliferation features of ccRCC cells by reducing cell glucose consumption, lactate production and cell proliferation. Further analysis by computer bioinformatics revealed that PKM2 is a target of miR-184. Both PKM2 mRNA and protein were significantly affected by addition of miR-184. Importantly, the PKM2 expression level was indeed increased in ccRCC samples, which is totally reverse compared to the decreased miR-184 expression level. Interestingly, we found that when PKM2 was knocked down in ccRCC cells, the rapid proliferation, high glucose consumption and high lactate production were all clearly inhibited, which indicates metabolic reprogramming and cancer progression blocking the in ccRCC cells. Our findings shed new light on ccRCC molecular study and provide a new and solid basis for developing ccRCC therapy.

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