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Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway.

Li Z, Li X, Wu S, Xue M, Chen W - Cancer Sci. (2014)

Bottom Line: Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers.In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an important mediator in this process.We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

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Long non-coding RNA UCA1 regulates glycolysis through hexokinase 2 (HK2) in stable bladder cancer cells. (a, c) Quantitative PCR analysis of HK2 mRNA levels in UMUC-2 cells transfected with pcDNA3.1/UCA1 (pcDNA-U) or pcDNA3.1/Mock (pcDNA-M) plasmids and 5637 cells transfected with pRNAT-U6.1/Neo-shUCA (pRNAT-U) and pRNAT-U6.1/Neo-Nc (pRNAT-N) plasmids. (a) Overexpression of UCA1. (c) Knockdown of UCA1. (b, d) Western blot analysis of HK2 protein level in stable cell lines with overexpression of UCA1 (b) or knockdown of UCA1 (d). (e, f) Glucose consumption (e) and lactate production (f) analysis in pcDNA-U cells transfected with HK2 siRNA or negative control (NC). The average values ± SD of three separate experiments were plotted. *P < 0.05.
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fig02: Long non-coding RNA UCA1 regulates glycolysis through hexokinase 2 (HK2) in stable bladder cancer cells. (a, c) Quantitative PCR analysis of HK2 mRNA levels in UMUC-2 cells transfected with pcDNA3.1/UCA1 (pcDNA-U) or pcDNA3.1/Mock (pcDNA-M) plasmids and 5637 cells transfected with pRNAT-U6.1/Neo-shUCA (pRNAT-U) and pRNAT-U6.1/Neo-Nc (pRNAT-N) plasmids. (a) Overexpression of UCA1. (c) Knockdown of UCA1. (b, d) Western blot analysis of HK2 protein level in stable cell lines with overexpression of UCA1 (b) or knockdown of UCA1 (d). (e, f) Glucose consumption (e) and lactate production (f) analysis in pcDNA-U cells transfected with HK2 siRNA or negative control (NC). The average values ± SD of three separate experiments were plotted. *P < 0.05.

Mentions: To probe the potential mechanism by which UCA1 regulates glycolysis in bladder cancer cells, we examined the effects of UCA1 on the expression of HK2. Quantitative PCR analyses showed that HK2 mRNA levels were upregulated by UCA1 (Fig. 2a). In line with these results, Western blot assays showed that UCA1 enhanced HK2 protein expression (Fig. 2b). Moreover, both HK2 mRNA and protein levels were significantly reduced by knockdown of UCA1 (Fig. 2c,d). Given that HK2 is a critical enzyme catalyzing the first and irreversible step of glycolysis,(16) and that its expression is most significantly regulated by UCA1, we reasoned that HK2 upregulation likely plays a major role in the enhancement of glucose consumption and lactate production under such conditions. Indeed, knockdown of HK2 significantly attenuated the effect of UCA1 on glucose consumption and lactate production (Fig. 2e,f). We thus focused on the regulation of HK2 for further mechanistic studies.


Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway.

Li Z, Li X, Wu S, Xue M, Chen W - Cancer Sci. (2014)

Long non-coding RNA UCA1 regulates glycolysis through hexokinase 2 (HK2) in stable bladder cancer cells. (a, c) Quantitative PCR analysis of HK2 mRNA levels in UMUC-2 cells transfected with pcDNA3.1/UCA1 (pcDNA-U) or pcDNA3.1/Mock (pcDNA-M) plasmids and 5637 cells transfected with pRNAT-U6.1/Neo-shUCA (pRNAT-U) and pRNAT-U6.1/Neo-Nc (pRNAT-N) plasmids. (a) Overexpression of UCA1. (c) Knockdown of UCA1. (b, d) Western blot analysis of HK2 protein level in stable cell lines with overexpression of UCA1 (b) or knockdown of UCA1 (d). (e, f) Glucose consumption (e) and lactate production (f) analysis in pcDNA-U cells transfected with HK2 siRNA or negative control (NC). The average values ± SD of three separate experiments were plotted. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig02: Long non-coding RNA UCA1 regulates glycolysis through hexokinase 2 (HK2) in stable bladder cancer cells. (a, c) Quantitative PCR analysis of HK2 mRNA levels in UMUC-2 cells transfected with pcDNA3.1/UCA1 (pcDNA-U) or pcDNA3.1/Mock (pcDNA-M) plasmids and 5637 cells transfected with pRNAT-U6.1/Neo-shUCA (pRNAT-U) and pRNAT-U6.1/Neo-Nc (pRNAT-N) plasmids. (a) Overexpression of UCA1. (c) Knockdown of UCA1. (b, d) Western blot analysis of HK2 protein level in stable cell lines with overexpression of UCA1 (b) or knockdown of UCA1 (d). (e, f) Glucose consumption (e) and lactate production (f) analysis in pcDNA-U cells transfected with HK2 siRNA or negative control (NC). The average values ± SD of three separate experiments were plotted. *P < 0.05.
Mentions: To probe the potential mechanism by which UCA1 regulates glycolysis in bladder cancer cells, we examined the effects of UCA1 on the expression of HK2. Quantitative PCR analyses showed that HK2 mRNA levels were upregulated by UCA1 (Fig. 2a). In line with these results, Western blot assays showed that UCA1 enhanced HK2 protein expression (Fig. 2b). Moreover, both HK2 mRNA and protein levels were significantly reduced by knockdown of UCA1 (Fig. 2c,d). Given that HK2 is a critical enzyme catalyzing the first and irreversible step of glycolysis,(16) and that its expression is most significantly regulated by UCA1, we reasoned that HK2 upregulation likely plays a major role in the enhancement of glucose consumption and lactate production under such conditions. Indeed, knockdown of HK2 significantly attenuated the effect of UCA1 on glucose consumption and lactate production (Fig. 2e,f). We thus focused on the regulation of HK2 for further mechanistic studies.

Bottom Line: Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers.In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an important mediator in this process.We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

Show MeSH
Related in: MedlinePlus