据韩联社报道，位于韩国光矫（地名）科技园的医药生物融合研究组日前谈称，其发现了导致肺癌的因子AIMP2-DX2。
该组称，AIMP2-DX2是AIMP2蛋白质的一种变异体，试验结果显示，注入AIMP2-DX2的18只白鼠中有14只患得肺癌，而对另外12只白鼠注入其他致癌物质的结果，只有4只患得肺癌，对已患肺癌的白鼠进行遏制AIMP2-DX2的结果，病情得到有效控制。
研究组对三星医疗院、庆北大学附属医院和美国Rosewell Park Cancel Institute(Buffalo, N.Y.)的97名肺癌患者进行了调研，发现肺癌的进展与AIMP2-DX2的增长密切相关，证实了AIMP2-DX2是治疗肺癌的重要目标因子。
该项研究结果已于本月1日刊登在《公共科学图书馆—遗传学》（PLoS Genetics）杂志上。（生物谷Bioon.com）
生物谷推荐原文出处：
PLoS Genet 7(3): e1001351. doi:10.1371/journal.pgen.1001351
Cancer-Associated Splicing Variant of Tumor Suppressor AIMP2/p38: Pathological Implication in Tumorigenesis
Jin Woo Choi1, Dae Gyu Kim1, Al-Eum Lee1, Hye Rim Kim1, Jin Young Lee1, Nam Hoon Kwon1, Young Kee Shin2, Soon-Kyung Hwang3, Seung-Hee Chang3, Myung-Haing Cho3, Yoon-La Choi4, Jhingook Kim5, Seung Hyun Oh6, Bora Kim6, Soo-Youl Kim6, Hyo-Sung Jeon7, Jae Yong Park8, Hyunseok Peter Kang9, Bum Joon Park10, Jung Min Han1,11, Sunghoon Kim1,11*
1 Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea, 2 Laboratory of Molecular Pathology, College of Pharmacy, Seoul National University, Seoul, Korea, 3 College of Veterinary Medicine, Seoul National University, Seoul, Korea, 4 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 5 Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 6 National Cancer Center, Research Institute, Goyang, Korea, 7 Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Korea, 8 Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea, 9 Department of Pathology and Laboratory Medicine, Roswell Cancer Park Institute, Buffalo, New York, United States of America, 10 Department of Molecular Biology, Pusan National University, Pusan, Korea, 11 WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Suwon, Korea
Abstract
Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target.
