Liu Min, Wu Haidong, Liu Tao, Li Yixuan, Wang Fang, Wan Haiying, Li Xin, Tang Hua
Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
Cell Res. 2009 Jul;19(7):828-37. doi: 10.1038/cr.2009.72.
MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the post-transcriptional level, and are deeply involved in the pathogenesis of several types of cancers. To investigate whether specific miRNAs and their target genes participate in the molecular pathogenesis of laryngeal carcinoma, oligonucleotide microarrays were used to assess the differential expression profiles of microRNAs and mRNAs in laryngeal carcinoma tissues compared with normal tissues. The oncogenic miRNA, microRNA-21 (miR-21), was found to be upregulated in laryngeal carcinoma tissues. Knockdown of miR-21 by specific antisense oligonucleotides inhibited the proliferation potential of HEp-2 cells, whereas overexpression of miR-21 elevated growth activity of the cells, as detected by the colony formation assay. The cell number reduction caused by miR-21 inhibition was due to the loss of control of the G1-S phase transition, instead of a noticeable increase in apoptosis. Subsequently, a new target gene of miR-21, BTG2, was found to be downregulated in laryngeal carcinoma tissues. BTG2 is known to act as a pan-cell cycle regulator and tumor suppressor. These findings indicate that aberrant expression of miR-21 may contribute to the malignant phenotype of laryngeal carcinoma by maintaining a low level of BTG2. The identification of the oncogenic miR-21 and its target gene, BTG2, in laryngeal carcinoma is potentially valuable for cancer diagnosis and therapy.
微小RNA是一类短的调节性RNA,可在转录后水平对基因表达进行负调控,并深度参与多种癌症的发病机制。为了研究特定的微小RNA及其靶基因是否参与喉癌的分子发病机制,利用寡核苷酸微阵列评估喉癌组织与正常组织中微小RNA和信使RNA的差异表达谱。致癌性微小RNA,即微小RNA-21(miR-21),在喉癌组织中被发现上调。通过特异性反义寡核苷酸敲低miR-21可抑制HEp-2细胞的增殖潜能,而miR-21的过表达则可提高细胞的生长活性,这通过集落形成试验得以检测。miR-21抑制导致的细胞数量减少是由于G1-S期转换失控,而非凋亡显著增加。随后,发现miR-21的一个新靶基因BTG2在喉癌组织中表达下调。已知BTG2可作为一种泛细胞周期调节因子和肿瘤抑制因子。这些发现表明,miR-21的异常表达可能通过维持低水平的BTG2而导致喉癌的恶性表型。在喉癌中鉴定致癌性miR-21及其靶基因BTG2对癌症诊断和治疗可能具有重要价值。