4.6 Article

Overexpression of PFKFB3 promotes cell glycolysis and proliferation in renal cell carcinoma

Journal

BMC CANCER
Volume 22, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12885-022-09183-2

Keywords

Renal cell carcinoma; PFKFB3; Glycolysis; Proliferation; G1; S transition

Categories

Funding

  1. National Nature Science Foundation of China [81772754]
  2. Major Basic Research and Cultivation Program of Natural Science Foundation of Guangdong Province [2017A03038009]
  3. Medical Science and Technology Foundation of Guangdong Province [A2019555]
  4. Shenzhen Basic Science Research [JCYJ20190809164617205]
  5. Sanming Project of Shenzhen [SZSM202011011]
  6. Research start-up fund of part-time PI, SAHSYSU [ZSQYJZPI202003]

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PFKFB3 is significantly up-regulated in RCC specimens and cell lines, correlating with later TNM stages and serving as a robust prognostic biomarker for ccRCC cases. PFKFB3 knockdown suppresses cell glycolysis, proliferation, and cell-cycle G1/S conversion in RCC cells. These results suggest PFKFB3 is a key molecular player in RCC progression and may serve as a potential therapeutic target against RCC.
Background Cancer cells prefer utilizing aerobic glycolysis in order to exacerbate tumor mass and maintain un-regulated proliferative rates. As a key glycolytic activator, phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) has been implicated in multiple tumor type progression. However, the specific function and clinical significance of PFKFB3 in renal cell carcinoma (RCC) are yet not clarified. This investigation assessed PFKFB3 roles in RCC. Methods PFKFB3 expression levels were analyzed in clear cell renal cell carcinoma (ccRCC) tissues, together with its relationship with clinical characteristics of ccRCC. Real-time PCR and Western blot assays were employed for determining PFKFB3 expression in different RCC cell lines. Furthermore, we determined the glycolytic activity by glucose uptake, lactate secretion assay and ECAR analysis. CCK-8 assay, clone formation, flow cytometry and EdU assessments were performed for monitoring tumor proliferative capacity and cell-cycle distribution. Furthermore, a murine xenograft model was employed for investigating the effect of PFKFB3 on tumor growth in vivo. Results PFKFB3 was significantly up-regulated in RCC specimens and cell lines in comparison to normal control. Overexpression of PFKFB3 was directly correlated to later TNM stages, thus becoming a robust prognostic biomarker for ccRCC cases. Furthermore, PFKFB3 knockdown suppressed cell glycolysis, proliferative rate and cell-cycle G1/S conversion in RCC cells. Importantly, in vivo experiments confirmed that PFKFB3 knockdown delayed tumor growth derived from the ACHN cell line. Conclusions Such results suggest that PFKFB3 is a key molecular player in RCC progression via mediating glycolysis / proliferation and provides a potential therapeutic target against RCC.

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