Browsing by Author "Huang, Tim"

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    A dynamic time order network for time-series gene expression data analysis
    (Springer Nature, 2012) Zhang, Pengyue; Mourad, Raphaël; Xiang, Yang; Huang, Kun; Huang, Tim; Nephew, Kenneth; Liu, Yunlong; Li, Lang; Center for Computational Biology and Bioinformatics, School of Medicine
    Background: Typical analysis of time-series gene expression data such as clustering or graphical models cannot distinguish between early and later drug responsive gene targets in cancer cells. However, these genes would represent good candidate biomarkers. Results: We propose a new model - the dynamic time order network - to distinguish and connect early and later drug responsive gene targets. This network is constructed based on an integrated differential equation. Spline regression is applied for an accurate modeling of the time variation of gene expressions. Then a likelihood ratio test is implemented to infer the time order of any gene expression pair. One application of the model is the discovery of estrogen response biomarkers. For this purpose, we focused on genes whose responses are late when the breast cancer cells are treated with estradiol (E2). Conclusions: Our approach has been validated by successfully finding time order relations between genes of the cell cycle system. More notably, we found late response genes potentially interesting as biomarkers of E2 treatment.
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    NF-κB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer.
    (Nature, 2016-10-13) Özeş, Ali R.; Miller, David F.; Özeş, Osman N.; Fang, Fang; Liu, Yunlong; Matei, Daniela; Huang, Tim; Nephew, Kenneth P.; Department of Cellular and Integrative Physiology, IU School of Medicine
    The transcription factor nuclear factor kappa B (NF-κB) and the long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) play diverse functional roles in cancer. In this study, we show that upregulation of HOTAIR induced platinum resistance in ovarian cancer, and increased HOTAIR levels were observed in recurrent platinum-resistant ovarian tumors vs. primary ovarian tumors. To investigate the role of HOTAIR during DNA damage induced by platinum, we monitored double-strand breaks and show that HOTAIR expression results in sustained activation of DNA damage response after platinum treatment. We demonstrate that ectopic expression of HOTAIR induces NF-κB activation during DNA damage response and MMP-9 and IL-6 expression, both key NF-κB target genes. We show that HOTAIR regulates activation of NF-κB by decreasing Iκ-Bα (NF-κB inhibitor) and establish that by inducing prolonged NF-κB activation and expression of NF-κB target genes during DNA damage, HOTAIR plays a critical role in cellular senescence and platinum sensitivity. Our findings suggest that a