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机构地区:[1]汕头大学医学院附属肿瘤医院乳腺中心广东省乳腺癌诊治研究重点实验室汕头大学医学院长江学者实验室,515041
出 处:《中华实验外科杂志》2017年第4期713-716,共4页Chinese Journal of Experimental Surgery
基 金:国家自然科学基金(81501539、81320108015、31271068);广东省自然科学基金(2015A030310211)
摘 要:RNA干扰(RNAi)是双链RNA分子诱发的基因沉默过程,可体现在转录水平或转录后水平。近年来,学者在细胞水平进行多基因组RNAi高通量筛选(HTS),研究包括乳腺癌在内的恶性肿瘤复杂的生物学行为和进展。构建高通量RNAi文库可特异性地筛选异常信号通路、揭示新型药物靶点、优化肿瘤综合治疗方案等,已成为研究肿瘤发生发展的有力工具。新近提出的“合成致死”策略联合RNAiHTS,也成功发现新的有效治疗靶点。乳腺癌是一种多基因、多分子径路参与,经过多阶段变化累积的全身性疾病,RNAiHTS技术的推广将有助于研究乳腺癌发生发展的复杂过程,探明其快速生长、侵袭及转移的潜在机制。基于此,本文概述了RNAiHTS技术的原理及其在乳腺癌基础和临床研究领域的最新应用。RNA interference (RNAi) is a gene silencing process induced by double-stranded RNA molecules’ binding to message RNA, at both transcriptional level and post-transcriptional level. Recently, high-throughput screening (HTS) with large-scale RNAi has been applied to the field of cancer research, including investigation of cancer development and progression. Especially, HTS with RNAi library was used to identify deregulated signaling pathway, to discover novel drug targets, and to optimize combination therapy and dosing schedule. Furthermore, "synthetic lethality" strategy is also combined with RNAi HTS to identify new drug targets. The development of breast cancer involves multiple factors, and is associated with multiple genetic alterations, and is a multi-step carcinogenesis process. The RNAi HTS might help to understand this complex process and underlying mechanism that collectively attribute to cancer cell invasion and metastasis. This article reviews the advancement of RNAi HTS assays, and focuses on its applications in both basic and translational research in breast cancer. A promising breakthrough is expected with RNAi HTS technology in the future.
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