Song Nan, Ma Xin, Li Hongzhao, Zhang Yu, Wang Xiaoxiong, Zhou Pingkun, Zhang Xu
Department of Urology, Chinese PLA General Hospital, Beijing, China.
Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, China.
Urol Oncol. 2015 May;33(5):205.e1-11. doi: 10.1016/j.urolonc.2015.02.003. Epub 2015 Mar 7.
MicroRNAs (miRNAs) are small RNAs with oncogenic and tumor-suppressing functions in cancer. miRNAs not only regulate various target genes but also participate in vital signaling pathways.
The tumor-suppressing function of miRNA-107 (miR-107) was confirmed in clear cell renal cell carcinoma in 52 paired clinical specimens and renal cell carcinoma cell lines. Significant correlations were noted between clinical features and miR-107 expression level. Lentiviral vector and biosynthesis mimics were used to overexpress pre-miR-107 or mimicked miR-107 to investigate further the tumorigenesis of miR-107 in vivo and in vitro. Cell proliferation and invasiveness were inhibited in the 786-O cell line after miR-107 was delivered. High miR-107 level expression can apparently induce cell cycle arrest at the G2/M phase and retard tumor growth in nude mice. In addition, eukaryotic translation initiation factor 5 was found to be a direct target of miR-107 and exhibited an inverse relationship with miR-107. It was seen that p53 and VHL genes, which are implicated in renal tumors, were associated with miR-107.
In summary, our results showed that miR-107 can inhibit cell proliferation and invasiveness of renal cell carcinoma. Furthermore, this study may provide a potential therapeutic regimen for clear cell renal cell carcinoma treatment.
微小RNA(miRNA)是一类在癌症中具有致癌和抑癌功能的小RNA。miRNA不仅调控各种靶基因,还参与重要的信号通路。
在52对临床标本和肾癌细胞系中证实了miRNA - 107(miR - 107)在透明细胞肾细胞癌中的抑癌功能。临床特征与miR - 107表达水平之间存在显著相关性。使用慢病毒载体和生物合成模拟物过表达前体miR - 107或模拟miR - 107,以进一步研究miR - 107在体内和体外的肿瘤发生情况。在递送miR - 107后,786 - O细胞系中的细胞增殖和侵袭能力受到抑制。高miR - 107水平表达明显可诱导细胞周期停滞在G2/M期,并延缓裸鼠肿瘤生长。此外,发现真核翻译起始因子5是miR - 107的直接靶标,且与miR - 107呈负相关。可见参与肾肿瘤的p53和VHL基因与miR - 107有关。
总之,我们的结果表明miR - 107可抑制肾细胞癌细胞的增殖和侵袭。此外,本研究可能为透明细胞肾细胞癌的治疗提供一种潜在的治疗方案。