中文摘要：

微RNAs（又称miRNAs或miRs）是一类长度为19~24个核苷酸的单链非编码RNA分子.miRNA通过与其靶向的mRNA分子序列特异性互补配对,调节mRNA表达水平,抑制转录后的蛋白质翻译.miRNA在肿瘤中既可作为致癌因子也可作为抑癌因子.本研究前期已报道miR-26b在前列腺癌细胞系中低表达,并且抑制细胞自噬.本研究进一步全面揭示miR-26b对前列腺肿瘤细胞的作用.我们发现过表达miR-26b能够在体外抑制前列腺癌细胞的增殖和侵袭,并抑制裸鼠体内原位异种前列腺肿瘤的生长.为了探究miR-26b对前列腺癌细胞增殖和侵袭的潜在调控机制,我们进行了表达谱芯片鉴定miR-26b调控基因.表达谱芯片分析表明,在前列腺癌细胞系PC-3中过表达miR-26b后,显著上调的基因57个,显著下调的基因55个（变化倍数均大于2,且P值小于0.05）.差异基因的功能多与细胞增殖、凋亡调控、蛋白质磷酸化和泛素化修饰调控过程相关,并且富集在多种信号通路中,例如TNF和TGF-茁信号通路.在这些筛选出的基因中,CEACAM6表达水平下调2.17倍;序列分析及实验验证表明,CEACAM6的3＇UTR区存在miR-26b的互补序列,是miR-26b的直接靶标.本研究证明了miR-26b能够靶向结合抑制CEACAM6的表达,从而抑制前列腺癌细胞在体外和体内的细胞增殖和侵袭活性,miR-26b是前列腺癌中的抑癌microRNA.

英文摘要：

microRNAs （miRNAs/miRs） are a class of single-stranded non-coding RNA molecules of 19-24 nucleotides in length. Via specific mR_NA complementary paring of target genes, miRNAs are able to regulate the expression of mRNA levels or inhibit protein translation following transcription, miRNAs can act as oncogenes or tumor suppressors. We have previously reported that miR-26b was expressed at a lower level in PCa cells compared to normal prostate cells and it inhibited autophagy. Here, we further revealed the role of miR-26b in prostate cancer cells. We found that over-expression of miR-26b suppressed prostate cancer cell proliferation, invasion and migration in vitro and inhibited the growth of prostate xenograft tumor in vivo. We have processed a gene expression microarray assay to investigate the concrete mechanism of miR-26b inhibition on prostate cancer cells proliferation and migration. We found that miR-26b significantly up-regulated 57 genes expression level, and simultaneously down-regulated 55 genes expression （fold change 〉2; P 〈 0.05） in PC-3. The differential genes were most associated with the regulation process of cell proliferation, apoptotic process, protein phosphorylation and ubiquitination respectively, and enriched in multiple pathways including TNF signaling pathway and TGF-13 signaling pathway. Among these filtered genes, CEACAM6 was significantly down regulated by miR-26b with a 2.17-fold. We identified a putative miR-26b binding site on 3＇UTR region of CEACAM6 and validated that miR-26b bound to the 3＇UTR region of CEACAM6 mRNA, suggesting that CEACAM6 is a direct target of miR-26b. Our results suggest that miR-26b suppresses cell proliferation by targeting CEACAM6 in PCa cells and miR-26b may be a candidate tumor-suppressor in prostate cancer.