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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 suppresses microRNA143 (miR143) to elevate hexokinase 2 (HK2) protein level in stable bladder cancer cells. (a, b, c) Quantitative PCR analysis of miR143 expression 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. (b) Knockdown of UCA1. (c) pcDNA-U cells were treated with rapamycin or DMSO. (d, e) Western blot analysis of HK2 protein level in stable cell lines. (d) pcDNA-U cells were transfected with miR143 mimic or negative control (NC). (e) pRNAT-U cells were transfected with miR143 inhibitor or NC. The average values ± SD of three separate experiments were plotted. *P < 0.05.
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fig04: Long non-coding RNA UCA1 suppresses microRNA143 (miR143) to elevate hexokinase 2 (HK2) protein level in stable bladder cancer cells. (a, b, c) Quantitative PCR analysis of miR143 expression 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. (b) Knockdown of UCA1. (c) pcDNA-U cells were treated with rapamycin or DMSO. (d, e) Western blot analysis of HK2 protein level in stable cell lines. (d) pcDNA-U cells were transfected with miR143 mimic or negative control (NC). (e) pRNAT-U cells were transfected with miR143 inhibitor or NC. The average values ± SD of three separate experiments were plotted. *P < 0.05.

Mentions: As recent findings suggested that miRNA143 (miR143), which is downregulated by mTOR activation, reduced glucose metabolism and inhibited cancer cell proliferation and tumor formation through targeting HK2,(21,27) we tested whether this regulation also extends to UCA1. Indeed, we found that miR143 expression was inversely correlated with UCA1 in stable cell lines (Fig. 4a,b), whereas rapamycin increased miR143 levels suppressed by UCA1 (Fig. 4c). We also found that the miR143 mimic significantly reduced the protein levels of HK2 (Fig. 4d), whereas miR143 inhibitor led to enhanced HK2 expression (Fig. 4e). These results suggested that UCA1 uses an additional mechanism to positively regulate HK2 protein expression at the post-transcriptional level.


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 suppresses microRNA143 (miR143) to elevate hexokinase 2 (HK2) protein level in stable bladder cancer cells. (a, b, c) Quantitative PCR analysis of miR143 expression 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. (b) Knockdown of UCA1. (c) pcDNA-U cells were treated with rapamycin or DMSO. (d, e) Western blot analysis of HK2 protein level in stable cell lines. (d) pcDNA-U cells were transfected with miR143 mimic or negative control (NC). (e) pRNAT-U cells were transfected with miR143 inhibitor or NC. The average values ± SD of three separate experiments were plotted. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317864&req=5

fig04: Long non-coding RNA UCA1 suppresses microRNA143 (miR143) to elevate hexokinase 2 (HK2) protein level in stable bladder cancer cells. (a, b, c) Quantitative PCR analysis of miR143 expression 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. (b) Knockdown of UCA1. (c) pcDNA-U cells were treated with rapamycin or DMSO. (d, e) Western blot analysis of HK2 protein level in stable cell lines. (d) pcDNA-U cells were transfected with miR143 mimic or negative control (NC). (e) pRNAT-U cells were transfected with miR143 inhibitor or NC. The average values ± SD of three separate experiments were plotted. *P < 0.05.
Mentions: As recent findings suggested that miRNA143 (miR143), which is downregulated by mTOR activation, reduced glucose metabolism and inhibited cancer cell proliferation and tumor formation through targeting HK2,(21,27) we tested whether this regulation also extends to UCA1. Indeed, we found that miR143 expression was inversely correlated with UCA1 in stable cell lines (Fig. 4a,b), whereas rapamycin increased miR143 levels suppressed by UCA1 (Fig. 4c). We also found that the miR143 mimic significantly reduced the protein levels of HK2 (Fig. 4d), whereas miR143 inhibitor led to enhanced HK2 expression (Fig. 4e). These results suggested that UCA1 uses an additional mechanism to positively regulate HK2 protein expression at the post-transcriptional level.

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