MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Export

@article{citeulike:3336198, abstract = {Tumor cells use preexisting prosurvival signaling pathways to evade the damaging and cytotoxic effects of anticancer agents. Radiation therapy is a primary form of cytotoxic anticancer treatment, but agents that successfully modify the radiation response in vivo are lacking. MicroRNAs (miRNA) are global gene regulators that play critical roles in oncogenesis and have been found to regulate prosurvival pathways. However, there is little understanding of how cellular miRNA expression affects the response of a cancer to cytotoxic therapy and ultimately outcome. The let-7 family of miRNAs regulates expression of oncogenes, such as RAS, and is specifically down-regulated in many cancer subtypes. In fact, low levels of let-7 predict a poor outcome in lung cancer. Here, we report that the let-7 family of miRNAs is overrepresented in a class of miRNAs exhibiting altered expression in response to radiation. More strikingly, we also can create a radiosensitive state when the select let-7 family of miRNAs is overexpressed in vitro in lung cancer cells and in vivo in a Caenorhabditis elegans model of radiation-induced cell death, whereas decreasing their levels causes radioresistance. In C. elegans, we show that this is partly through control of the proto-oncogene homologue let-60/RAS and genes in the DNA damage response pathway. These findings are the first direct evidence that miRNAs can suppress resistance to anticancer cytotoxic therapy, a common feature of cancer cells, and suggest that miRNAs may be a viable tool to augment current cancer therapies.}, author = {Weidhaas, J. B. and Babar, I. and Nallur, S. M. and Trang, P. and Roush, S. and Boehm, M. and Gillespie, E. and Slack, F. J.}, citeulike-article-id = {3336198}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/18056433}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=18056433}, citeulike-linkout-2 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00031300}, journal = {Cancer Res}, keywords = {article, b03954, c05g56, c\_elegans, caenorhabditis\_elegans, cdc-253, celegans, coh-1, elegans, f56a123, fcd-2, k08a83, let-60, let-7, lin-58, mir-84, nematode, rad-51, wormbase, y41e39, y43c5a6, zk63711, zk7926}, pages = {11111--11116}, posted-at = {2008-09-25 15:19:17}, priority = {3}, title = {MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18056433}, volume = {67}, year = {2007} }

TY - JOUR ID - citeulike:3336198 L3 - citeulike-article-id:3336198 N2 - Tumor cells use preexisting prosurvival signaling pathways to evade the damaging and cytotoxic effects of anticancer agents. Radiation therapy is a primary form of cytotoxic anticancer treatment, but agents that successfully modify the radiation response in vivo are lacking. MicroRNAs (miRNA) are global gene regulators that play critical roles in oncogenesis and have been found to regulate prosurvival pathways. However, there is little understanding of how cellular miRNA expression affects the response of a cancer to cytotoxic therapy and ultimately outcome. The let-7 family of miRNAs regulates expression of oncogenes, such as RAS, and is specifically down-regulated in many cancer subtypes. In fact, low levels of let-7 predict a poor outcome in lung cancer. Here, we report that the let-7 family of miRNAs is overrepresented in a class of miRNAs exhibiting altered expression in response to radiation. More strikingly, we also can create a radiosensitive state when the select let-7 family of miRNAs is overexpressed in vitro in lung cancer cells and in vivo in a Caenorhabditis elegans model of radiation-induced cell death, whereas decreasing their levels causes radioresistance. In C. elegans, we show that this is partly through control of the proto-oncogene homologue let-60/RAS and genes in the DNA damage response pathway. These findings are the first direct evidence that miRNAs can suppress resistance to anticancer cytotoxic therapy, a common feature of cancer cells, and suggest that miRNAs may be a viable tool to augment current cancer therapies. JF - Cancer Res EP - 11116 TI - MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. VL - 67 SP - 11111 KW - article KW - b03954 KW - c05g56 KW - c_elegans KW - caenorhabditis_elegans KW - cdc-253 KW - celegans KW - coh-1 KW - elegans KW - f56a123 KW - fcd-2 KW - k08a83 KW - let-60 KW - let-7 KW - lin-58 KW - mir-84 KW - nematode KW - rad-51 KW - wormbase KW - y41e39 KW - y43c5a6 KW - zk63711 KW - zk7926 AU - Weidhaas, JB AU - Babar, I AU - Nallur, SM AU - Trang, P AU - Roush, S AU - Boehm, M AU - Gillespie, E AU - Slack, FJ PY - 2007/// UR - http://view.ncbi.nlm.nih.gov/pubmed/18056433 ER -