RNA异常与肿瘤调控研究进展

Dysregulation of RNA in cancer

肿瘤的发生是一个多因素、多步骤的过程,其根本原因是细胞稳态的失衡。近年研究发现,在肿瘤的发生、发展中除了蛋白质功能紊乱、DNA突变之外,还存在着大量RNA的异常,包括异常的microRNA(miRNA)、长链非编码RNA(long non-coding RNA,lncRNA)、循环RNA等;此外,肿瘤细胞中还存在RNA转录、加工及调控功能的异常,如RNA选择性剪接、RNA编辑、竞争性内源RNA调控等。这些非编码RNA可以在转录后水平及表观遗传学水平调控癌基因和抑癌基因的功能,影响肿瘤的发生和发展,是肿瘤诊断、治疗及预后判断的潜在靶标。竞争性内源RNA使得lncRNA与mRNA通过miRNA相互调控,以"miRNA结合位点"为媒介,形成RNA调控网络。RNA选择性剪接使得癌基因或抑癌基因产生功能异常的转录本,进而影响其生物学功能。肿瘤中究竟哪些机制导致这些RNA表达及功能的异常,RNA表达及功能的异常又如何影响肿瘤的发生和发展,有哪些表达或功能异常的RNA可以作为肿瘤诊断及预后判断的标志物,又有哪些RNA可以作为肿瘤靶向治疗的靶标?等等问题亟待深入探讨,RNA异常与肿瘤调控已成为肿瘤研究的前沿热点领域。

The development of cancer is a complex nmhistage process, which is primarily due to the unbalance of cellular homeostasis. In addition to the well- characlerized protein coding dysfunction and DNA muta- tion, dysregulation of ram-coding RNAs including microR- NA （miRNA）, long non-coding RNA （lncRNA） and cir- culating miRNA was found in the initiation and progression of cancer. Moreover, aberrant RNA transcription, pro- cessing and regulation, such RNA editing and competing as RNA ahernative endogenous RNA re splicing, gulation, have, emerged as important regulatory molecules or mecha- nisnls in cancer cells. These non-coding RNAs may play vital roles in tumorigenesis by regulating oncogene and tumor suppressor gene at either post-transcriptional level or epigenetic level, and act as potential targets for tumor diagnosis, prognosis and cancer therapy. Through compe- ting endogenous RNA, the lncRNA cross-talk with mRNA in a miRNA-dependent manner, and this form a regulatory network. Via RNA alternative splicing, onco- gene and tumor-suppressor gene couht generate tumor-spe-cific alternative-splicing transcripts, and therefore affect their biological functions. However, several questions re- main to be elucidated： What are the underlying mecha- nisms of abnormal expression pattern and dysregulation of RNA in cancer？ How do the aberrant expression and func- tion of RNAs affect tumorigenesis and progression？ Which abnormal RNA can be used as a biomarker for tumor diag- nosis, prognosis, as well as the therapeutic target for cancers？ Taken together, RNA dysregulation in cancer has become a new research frontier in cancer research.