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MicroRNA-411 Downregulation Enhances Tumor Growth by Upregulating MLLT11 Expression in Human Bladder Cancer
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2018-03-10 , DOI: 10.1016/j.omtn.2018.03.003
Honglei Jin , Wenrui Sun , Yuanmei Zhang , Huiying Yan , Huating Liufu , Shuai Wang , Caiyi Chen , Jiayan Gu , Xiaohui Hua , Lingli Zhou , Guosong Jiang , Dapang Rao , Qipeng Xie , Haishan Huang , Chuanshu Huang

Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in bladder cancer growth are not explored yet at present. Here, we screened 1,900 known miRNAs and first discovered that miR-411 was one of the major miRNAs, which was down-regulated in n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCs. This miR-411 down-regulation was also observed in human BC tissues and cell lines. The results from evaluating the relationship between miR-411 and patient survival in BC using the TCGA (The Cancer Genome Atlas) database indicated that miR-411 was positively correlated with DFS (disease-free survival). Our studies also showed that miR-411 inhibited tumor growth of human BC cells in a xenograft animal model. Mechanistic studies revealed that overexpression of miR-411 repressed the expression of ALL1-fused gene from the chromosome 1q (AF1q) (MLLT11) by binding to the 3′ untranslated region (UTR) of mllt11 mRNA and in turn induced p21 expression and caused cell cycle arrest at the G2/M phase, further inhibiting BC tumor growth. Collectively, our results improve our understanding of the role of miR-411 in BC tumor growth and suggest miR-411 and MLLT11 as potential new targets for the treatment of BC patients.



中文翻译:

MicroRNA-411下调通过上调人膀胱癌中MLLT11的表达来增强肿瘤的生长

尽管先前的一些研究已经报道了各种微RNA(miRNA)在调节人类膀胱癌(BC)发育中的意义,但目前尚未探索许多miRNA的改变和功能在膀胱癌生长中的作用。在这里,我们筛选了1,900个已知的miRNA,并首先发现miR-411是主要的miRNA之一,在正丁基-N-(4-羟丁基)-亚硝胺(BBN)诱导的BC中被下调。在人BC组织和细胞系中也观察到了miR-411的下调。使用TCGA(癌症基因组图谱)数据库评估miR-411与BC患者生存率之间的关系的结果表明,miR-411与DFS(无疾病生存率)呈正相关。我们的研究还表明,miR-411在异种移植动物模型中抑制人BC细胞的肿瘤生长。AF1q)(MLLT11)通过与mllt11 mRNA的3'非翻译区(UTR)结合,进而诱导p21表达并导致细胞周期停滞在G2 / M期,从而进一步抑制了BC肿瘤的生长。总的来说,我们的结果增进了我们对miR-411在BC肿瘤生长中作用的理解,并建议miR-411和MLLT11作为治疗BC患者的潜在新靶标。

更新日期:2018-03-10
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