Description of Research
The human genome contains ~25,000 protein-coding genes representing less than 2% of the total genome, whereas up to 70% of the human genome is transcribed to RNA, yielding many thousands of non-coding RNAs. The recent discovery of non-coding RNA genes has dramatically altered our understanding on cancer. Long non-coding RNAs (lncRNAs) are operationally defined as RNA genes larger than 200 nucleotide that do not appear to have protein coding potential. micoRNAs (miRNAs) are endogenous ~18-25 nucleotide non-coding small RNAs which regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or the inhibition of protein translation. The Zhang laboratory is interested in molecular mechanisms of non-coding RNAs (microRNA and lncRNA) in tumorigenesis, and the potential application of non-coding RNA in treatment for breast and ovarian cancer. High-throughput profiling technologies (microarray and deep-sequencing) and whole-genome wide miRNA/siRNA screening are used in the laboratory.
OncoGenome and EpiGenome in ovarian and breast cancers
microRNAs/long non-coding RNAs in cancer
microRNA-based therapeutic and diagnostic strategies in cancer
microRNAs in cancer stem cells and embryonic stem cells
Hu Xiaowen, Feng Yi, Zhang Dongmei, Zhao Sihai D, Hu Zhongyi, Greshock Joel, Zhang Youyou, Yang Lu, Zhong Xiaomin, Wang Li-Ping, Jean Stephanie, Li Chunsheng, Huang Qihong, Katsaros Dionyssios, Montone Kathleen T, Tanyi Janos L, Lu Yiling, Boyd Jeff, Nathanson Katherine L, Li Hongzhe, Mills Gordon B, Zhang Lin: A Functional Genomic Approach Identifies FAL1 as an Oncogenic Long Noncoding RNA that Associates with BMI1 and Represses p21 Expression in Cancer. Cancer cell 26(3): 344-57, Sep 2014.
Li Ning, Kaur Sippy, Greshock Joel, Lassus Heini, Zhong Xiaomin, Wang Yanling, Leminen Arto, Shao Zhongjun, Hu Xiaowen, Liang Shun, Katsaros Dionyssios, Huang Qihong, Bützow Ralf, Weber Barbara L, Coukos George, Zhang Lin: A combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancer. Cancer research 72(1): 154-64, Jan 2012.
Li Ning, Zhong Xiaomin, Lin Xiaojuan, Guo Jinyi, Zou Lian, Tanyi Janos L, Shao Zhongjun, Liang Shun, Wang Li-Ping, Hwang Wei-Ting, Katsaros Dionyssios, Montone Kathleen, Zhao Xia, Zhang Lin: Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer. The Journal of biological chemistry 287(21): 17386-97, May 2012.
Facciabene Andrea, Peng Xiaohui, Hagemann Ian S, Balint Klara, Barchetti Andrea, Wang Li-Ping, Gimotty Phyllis A, Gilks C Blake, Lal Priti, Zhang Lin, Coukos George: Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 475(7355): 226-30, Jul 2011.
Yang Xiaojun, Lin Xiaojuan, Zhong Xiaomin, Kaur Sippy, Li Ning, Liang Shun, Lassus Heini, Wang Liping, Katsaros Dionyssios, Montone Kathleen, Zhao Xia, Zhang Youcheng, Bützow Ralf, Coukos George, Zhang Lin: Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. Cancer research 70(22): 9463-72, Nov 2010.
Zhong Xiaomin, Li Ning, Liang Shun, Huang Qihong, Coukos George, Zhang Lin: Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. The Journal of biological chemistry 285(53): 41961-71, Dec 2010.
Gumireddy Kiranmai, Li Anping, Gimotty Phyllis A, Klein-Szanto Andres J, Showe Louise C, Katsaros Dionyssios, Coukos George, Zhang Lin, Huang Qihong: KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer. Nature cell biology 11(11): 1297-304, Nov 2009.
Yang Nuo, Kaur Sippy, Volinia Stefano, Greshock Joel, Lassus Heini, Hasegawa Kosei, Liang Shun, Leminen Arto, Deng Shan, Smith Lori, Johnstone Cameron N, Chen Xian-Ming, Liu Chang-Gong, Huang Qihong, Katsaros Dionyssios, Calin George Adrian, Weber Barbara L, Bützow Ralf, Croce Carlo M, Coukos George, Zhang Lin: MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer research 68(24): 10307-14, Dec 2008.
Zhang Lin, Huang Jia, Yang Nuo, Greshock Joel, Megraw Molly S, Giannakakis Antonis, Liang Shun, Naylor Tara L, Barchetti Andrea, Ward Michelle R, Yao George, Medina Angelica, O'brien-Jenkins Ann, Katsaros Dionyssios, Hatzigeorgiou Artemis, Gimotty Phyllis A, Weber Barbara L, Coukos George: microRNAs exhibit high frequency genomic alterations in human cancer. Proceedings of the National Academy of Sciences of the United States of America 103(24): 9136-41, Jun 2006.
Zhang Lin, Conejo-Garcia Jose R, Katsaros Dionyssios, Gimotty Phyllis A, Massobrio Marco, Regnani Giorgia, Makrigiannakis Antonis, Gray Heidi, Schlienger Katia, Liebman Michael N, Rubin Stephen C, Coukos George: Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. The New England journal of medicine 348(3): 203-13, Jan 2003.
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Last updated: 04/09/2015
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