@article {226, title = {Elevated expression of UBE2T exhibits oncogenic properties in human prostate cancer.}, journal = {Oncotarget}, volume = {6}, year = {2015}, month = {2015 Sep 22}, pages = {25226-39}, abstract = {

Increased expression of ubiquitin-conjugating enzyme E2T (UBE2T) is reported in human prostate cancer. However, whether UBE2T plays any functional role in prostate cancer development remains unknown. We here report the first functional characterization of UBE2T in prostate carcinogenesis. Prostate cancer tissue array analysis confirmed upregulation of UBE2T in prostate cancer, especially these with distant metastasis. Moreover, higher level of UBE2T expression is associated with poorer prognosis of prostate cancer patients. Ectopic expression of UBE2T significantly promotes prostate cancer cell proliferation, motility and invasion, while UBE2T depletion by shRNA significantly inhibits these abilities of prostate cancer cells. Xenograft mouse model studies showed that overexpression of UBE2T promotes whereas UBE2T depletion inhibits tumor formation and metastasis significantly. Collectively, we identify critical roles of UBE2T in prostate cancer development and progression. These findings may serve as a framework for future investigations designed to more comprehensive determination of UBE2T as a potential therapeutic target.

}, keywords = {Cell Line, Tumor, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Heterografts, Humans, Kaplan-Meier Estimate, Male, Neoplasm Invasiveness, Neoplasm Transplantation, Prognosis, Prostatic Neoplasms, RNA Interference, Signal Transduction, Time Factors, Transfection, Ubiquitin-Conjugating Enzymes, Up-Regulation}, issn = {1949-2553}, doi = {10.18632/oncotarget.4712}, author = {Wen, Mingxin and Kwon, Yongwon and Wang, Yongsheng and Jiang-Hua Mao and Wei, Guangwei} } @article {224, title = {FBXW7 negatively regulates ENO1 expression and function in colorectal cancer.}, journal = {Lab Invest}, volume = {95}, year = {2015}, month = {2015 Sep}, pages = {995-1004}, abstract = {

FBXW7 (F-box and WD40 domain protein 7) is a tumor suppressor frequently inactivated in human cancers. The precise molecular mechanisms by which FBXW7 exerts antitumor activity remain under intensive investigation and are thought to relate in part to FBXW7-mediated destruction of key cancer-relevant proteins. Enolase 1 (ENO1) possesses oncogenic activity and is often overexpressed in various human cancers, besides its critical role in glycolysis. However, the detailed regulatory mechanisms of ENO1 expression remain unclear. Here we show that the elevated expression of ENO1 was identified in FBXW7-depletion HCT116 cells through two-dimensional protein electrophoresis and mass spectrometry assays (2DE-MS). Subsequent western blotting and immunohistochemical assays confirmed that ENO1 expression reversely correlates with FBXW7 expression in several cells and colon cancer tissues. Furthermore, we show that FBXW7 physically binds to ENO1 and targets ENO1 for ubiquitin-mediated degradation. Functionally, we found that FBXW7 suppresses the ENO1-induced gene expression, lactate production, cell proliferation and migration. These findings suggest that ENO1 is a novel substrate of FBXW7, and its activity can be negatively regulated by FBXW7 at the posttranslational level. Our work provides a novel molecular insight into FBXW7-directed tumor suppression through regulation of ENO1.

}, keywords = {Biomarkers, Tumor, Blotting, Western, Cell Cycle Proteins, Colorectal Neoplasms, DNA Primers, DNA-Binding Proteins, Electrophoresis, Gel, Two-Dimensional, F-Box Proteins, Gene Expression Regulation, Neoplastic, HCT116 Cells, Humans, Immunohistochemistry, Mass Spectrometry, Phosphopyruvate Hydratase, Real-Time Polymerase Chain Reaction, Regression Analysis, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases}, issn = {1530-0307}, doi = {10.1038/labinvest.2015.71}, author = {Zhan, Panpan and Wang, Yuli and Zhao, Shihu and Liu, Chunyan and Wang, Yunshan and Wen, Mingxin and Jiang-Hua Mao and Wei, Guangwei and Zhang, Pengju} } @article {206, title = {CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression.}, journal = {Cancer Res}, volume = {74}, year = {2014}, month = {2014 Jan 15}, pages = {520-31}, abstract = {

The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells.

}, keywords = {Animals, Breast, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, Cullin Proteins, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Histones, Homeodomain Proteins, Humans, Kruppel-Like Transcription Factors, Mammary Neoplasms, Experimental, Mice, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Promoter Regions, Genetic, Signal Transduction, Transcription Factors}, issn = {1538-7445}, doi = {10.1158/0008-5472.CAN-13-2182}, author = {Wang, Yunshan and Wen, Mingxin and Kwon, Yongwon and Xu, Yangyang and Liu, Yueyong and Zhang, Pengju and He, Xiuquan and Wang, Qin and Huang, Yurong and Jen, Kuang-Yu and LaBarge, Mark A and You, Liang and Kogan, Scott C and Gray, Joe W and Jiang-Hua Mao and Wei, Guangwei} } @article {211, title = {CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to erlotinib via transcriptional regulation of EGFR.}, journal = {Mol Cancer}, volume = {13}, year = {2014}, month = {2014}, pages = {252}, abstract = {

BACKGROUND: CUL4A has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear.

METHODS: Expression level of CUL4A was examined by RT-PCR and Western blot. Forced expression of CUL4A was mediated by retroviruses, and CUL4A silencing by shRNAs expressing lentiviruses. Growth capacity of lung cancer cells was measured by MTT in vitro and tumorigenesis in vivo, respectively.

RESULTS: We found that CUL4A was highly expressed in human lung cancer tissues and lung cancer cell lines, and this elevated expression positively correlated with disease progression and prognosis. Overexpression of CUL4A in human lung cancer cell lines increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance to chemotherapy. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Mechanistically, we revealed CUL4A regulated EGFR transcriptional expression and activation, and subsequently activated AKT. Targeted inhibition of EGFR activity blocked these CUL4A induced oncogenic activities.

CONCLUSIONS: Our results highlight the significance of CUL4A in NSCLC and suggest that CUL4A could be a promising therapy target and a potential biomarker for prognosis and EGFR target therapy in NSCLC patients.

}, keywords = {Apoptosis, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Cell Proliferation, Cullin Proteins, Erlotinib Hydrochloride, Female, Humans, Lung Neoplasms, Male, Middle Aged, Protein Kinase Inhibitors, Quinazolines, Receptor, Epidermal Growth Factor, Transcription, Genetic}, issn = {1476-4598}, doi = {10.1186/1476-4598-13-252}, author = {Wang, Yunshan and Zhang, Pengju and Liu, Ziming and Wang, Qin and Wen, Mingxin and Wang, Yuli and Yuan, Hongtu and Jiang-Hua Mao and Wei, Guangwei} } @article {202, title = {C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes.}, journal = {Epigenetics}, volume = {8}, year = {2013}, month = {2013 Jun}, pages = {571-83}, abstract = {

Recently, it has been suggested that C2ORF40 is a candidate tumor suppressor gene in breast cancer. However, the mechanism for reduced expression of C2ORF40 and its functional role in breast cancers remain unclear. Here we show that C2ORF40 is frequently silenced in human primary breast cancers and cell lines through promoter hypermethylation. C2ORF40 mRNA level is significantly associated with patient disease-free survival and distant cancer metastasis. Overexpression of C2ORF4 0 inhibits breast cancer cell proliferation, migration and invasion. By contrast, silencing C2ORF40 expression promotes these biological phenotypes. Bioinformatics and FACS analysis reveal C2ORF40 functions at G2/M phase by downregulation of mitotic genes expression, including UBE2C. Our results suggest that C2ORF40 acts as a tumor suppressor gene in breast cancer pathogenesis and progression and is a candidate prognostic marker for this disease.

}, keywords = {Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, DNA Methylation, Female, Gene Expression Regulation, Neoplastic, Genes, cdc, Genes, Tumor Suppressor, Humans, Mitosis, Neoplasm Invasiveness, Neoplasm Proteins, Prognosis}, issn = {1559-2308}, doi = {10.4161/epi.24626}, author = {Lu, Jing and Wen, Mingxin and Huang, Yurong and He, Xiuquan and Wang, Yunshan and Wu, Qi and Li, Zengchun and Castellanos-Mart{\'\i}n, Andr{\'e}s and Abad, Mar and Cruz-Hernandez, Juan J and Rodriguez, Cesar A and Perez-Losada, Jesus and Jiang-Hua Mao and Wei, Guangwei} }