Abstract
Osteosarcoma is the most common primary malignant tumor in children and young adults, and the molecular regulation of the invasion of osteosarcoma (OS) remains unknown. In this study, we found that increased expression of ALX1 was associated with the progression of osteosarcoma and that ALX1 protein levels were significantly elevated in matched distant metastases. High ALX1 levels also predict shorter overall survival of osteosarcoma patients. We investigated the therapeutic potential of targeting ALX1 expression using the technique of RNA silencing via short hairpin RNA (shRNA). Synthetic shRNA duplexes against ALX1 were introduced to downregulate the expression of ALX1 in a highly malignant osteosarcoma cell line, U2OS. The results obtained indicated that shRNA targeting of ALX1 could lead to an efficient and specific inhibition of endogenous ALX1 activity. Furthermore, we found that depletion of ALX1 caused a dramatic cell cycle arrest, followed by massive apoptotic cell death, and eventually resulted in a significant decrease in migration and invasion of the osteosarcoma cell line studied.
References
Feb 3, 1993·Journal of the National Cancer Institute·D C AllredW L McGuire
Nov 11, 2003·Journal of Pediatric Hematology/oncology·Richard Gorlick, Paul A Meyers
Feb 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bernard PerbalKatia Scotlandi
Sep 9, 2008·The International Journal of Biochemistry & Cell Biology·Chih-Chiun Chen, Lester F Lau
Oct 22, 2008·Molecular Biology Reports·Saminathan S NathanAndre J van Wijnen
Apr 8, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Emilios E PakosJohn P A Ioannidis
Sep 29, 2009·Expert Opinion on Investigational Drugs·Koren K MannWilson H Miller
Sep 18, 2010·Neoplasma·Y F WuH Y Shen
Oct 29, 2010·Journal of Orthopaedic Surgery and Research·Valerie A Siclari, Ling Qin
Mar 8, 2011·Journal of Experimental & Clinical Cancer Research : CR·Qinghua ZhaoJiwei Tian
Mar 26, 2011·Sarcoma·Sharon A Savage, Lisa Mirabello
Jan 5, 2013·Cancer Research·Hong YuanTakeshi Senga
Aug 7, 2013·Oncology Reports·Yueliang LiuJinyong Luo
May 13, 2014·Cancer Science·Qiang MeiHaidong Xu
May 20, 2014·Journal of Evolutionary Biology·L W SimmonsM Almbro
Sep 18, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qiang WangJianning Zhao
Oct 5, 2014·Cellular Signalling·Haiyu LiFangzhou Song
Citations
Jun 26, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Tieyi HuYi You
Aug 29, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Jingwei ZhaoBo Wei
May 21, 2021·Frontiers in Cell and Developmental Biology·Haiyan LiuJialiang Yang