Calin G A, Croce C M
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
Oncogene. 2006 Oct 9;25(46):6202-10. doi: 10.1038/sj.onc.1209910.
Over the past five decades, a plethora of nonrandom chromosomal abnormalities have been consistently reported in malignant cells facilitating the identification of cancer-associated protein coding oncogenes and tumor suppressors. The genetic dissection of hot spots for chromosomal abnormalities in the age of the sequenced human genome resulted in the discovery that microRNA (miRNA) genes, encoding for a class of small noncoding RNAs, frequently resides in such genomic regions. The combination of nonrandom chromosomal abnormalities and other types of genetic alterations or epigenetic events contribute to downregulation or overexpression of miRNAs. The consequent abnormal expression of miRNAs affect cell cycle, survival and differentiation programs and selective targeting of these noncoding genes could provide novel therapeutic options for killing the malignant cells.
在过去的五十年里，恶性细胞中持续报道了大量非随机染色体异常情况，这有助于识别与癌症相关的蛋白质编码癌基因和肿瘤抑制基因。在人类基因组测序时代，对染色体异常热点区域的基因剖析发现，编码一类小非编码RNA的微小RNA（miRNA）基因经常位于此类基因组区域。非随机染色体异常与其他类型的基因改变或表观遗传事件相结合，导致miRNA的下调或上调。miRNA的异常表达会影响细胞周期、存活和分化程序，而选择性靶向这些非编码基因可能为杀死恶性细胞提供新的治疗选择。
