Ye Wang

Publications (2)12.63 Total impact

• Article: The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss.

  Yan Feng, Ye Wang, Zuoyun Wang, Zhaoyuan Fang, Fei Li, Yijun Gao, Hongyan Liu, Tian Xiao, Fuming Li, Yang Zhou, Qiwei Zhai, Xiaolong Liu, Yihua Sun, Nabeel Bardeesy, Kwok-Kin Wong, Haiquan Chen, Zhi-Qi Xiong, Hongbin Ji
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  ABSTRACT: Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Here we demonstrate that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process. Mechanistically, LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of its suppressor CRTC1 from the nucleus. Notably, ectopic expression of either NEDD9 or CRTC1 partially reversed the inhibitory function of LKB1 on metastasis of lung cancer cells. In clinical specimens, elevated expression of NEDD9 was associated with malignant progression and metastasis. Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes.
  Cancer Research 10/2012; · 7.86 Impact Factor
• Article: MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene.

  Rong Fang, Tian Xiao, Zhaoyuan Fang, Yihua Sun, Fei Li, Yijun Gao, Yan Feng, Li Li, Ye Wang, Xiaolong Liu, Haiquan Chen, Xin-Yuan Liu, Hongbin Ji
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  ABSTRACT: High glycolysis, well known as "Warburg effect," is frequently observed in a variety of cancers. Whether the deregulation of miRNAs contributes to the Warburg effect remains largely unknown. Because miRNA regulates gene expression at both mRNA and protein levels, we constructed a gene functional association network, which allows us to detect the gene activity instead of gene expression, to integratively analyze the microarray data for gene expression and miRNA expression profiling and identify glycolysis-related gene-miRNA pairs deregulated in cancer. Hexokinase 2 (HK2), coding for the first rate-limiting enzyme of glycolysis, is among the top list of genes predicted and potentially regulated by multiple miRNAs including miR-143. Interestingly, miR-143 expression was inversely associated with HK2 protein level but not mRNA level in human lung cancer samples. miR-143, down-regulated by mammalian target of rapamycin activation, reduces glucose metabolism and inhibits cancer cell proliferation and tumor formation through targeting HK2. Collectively, we have not only established a novel methodology for gene-miRNA pair prediction but also identified miR-143 as an essential regulator of cancer glycolysis via targeting HK2.
  Journal of Biological Chemistry 05/2012; 287(27):23227-35. · 4.77 Impact Factor