肿瘤精准治疗新策略——靶向调控DNA损伤修复功能的长链非编码RNA

A novel strategy in precision medicine-targeting DNA damage repair pathway regulating long non-coding RNA

在过去的10年中,随着高通量测序技术的快速发展,在肿瘤中数以万计的长链非编码RNA(long non-coding RNA,lncRNA)转录子被转录组测序发现。然而,绝大多数lncRNA的全长序列和作用机制尚不清楚,明确这些lncRNA的功能是一项极具挑战性的工作。DNA损伤修复(DNA damage repair,DDR)在肿瘤耐药中的机制,以及利用DDR功能异常的“协同致死”治疗策略已成为目前的研究热点。近年的研究发现,lncRNA通过参与肿瘤相关信号通路的调控而影响肿瘤的发生发展、放化疗和靶向治疗效果。其中,DDR修复机制会直接影响放化疗效果。已有少数研究发现,lncRNA直接或间接参与DDR功能的调控,如何针对lncRNA异常表达导致肿瘤细胞DDR功能缺失发展新的治疗策略,将是极具应用前景的研究方向。

Over the last decade,thousands of long non-coding RNAs(lncRNAs)were found aberrantly expressed in cancers by high-throughput sequencing.However,it is a major challenge to discern the functional noncoding transcripts from a vast transcriptome and obtain the full-length sequences.It is still in the infant stage of understanding the role of the tremendous number of lncRNAs.DNA damage repair(DDR)involves in carcinogenesis and the resistance of chemo-radiotherapy.The′synthetic lethality′therapeutic strategy is based on DDR defects of cancer.A limited number of lncRNAs have been found to regulate DDR and other cancer-related signaling pathways directly or indirectly.It is a promsing direction to discern the roles and mechanisms of lncRNAs in DDR,and further to investigate therapeutic values of aberrant expressed lncRNAs in cancers.