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The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1

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OP-NARE130182 4976..4987 LncRNA loc285194 is a p53-regulated tumor suppressor Qian Liu1,2, Jianguo Huang1,3, Nanjiang Zhou1,3, Ziqiang Zhang3, Ali Zhang1, Zhaohui Lu4, Fangting Wu5,* and Yin-Yuan Mo1,3,* 1Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA, 2Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, PR China, 3Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA, 4Department of Endocrinology, PLA General Hospital, Beijing 100853, PR China and 5System Biosciences, Mountain View, CA, USA Received November 9, 2012; Revised February 24, 2013; Accepted February 26, 2013 ABSTRACT Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding RNAs including long non-coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer pro- gression and metastasis. LncRNA loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regu- lation of loc285194. Moreover, the underlying mech- anism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo. Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of miR-211. We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer speci- men

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