MiR-194 deregulation contributes to colorectal carcinogenesis via targeting AKT2 pathway.
MiR-194 deregulation contributes to colorectal carcinogenesis via targeting AKT2 pathway.
复制标题
MiR-194 失调通过靶向 AKT2 通路促进结直肠癌发生。
作者：
Zhao HJ;Ren LL;Wang ZH;Sun TT;Yu YN;Wang YC;Yan TT;Zou W;He J;Zhang Y;Hong J;Fang JY
翻译后摘要：最近的研究越来越多地将microRNA与结直肠癌（CRC）联系起来。据报道，miR-194在不同的肿瘤类型中失调，而miR-194在CRC中的功能在很大程度上仍未探索。本文探讨了miR-194的生物学效应、作用机制和临床意义。功能分析显示，miR-194的过表达在体外抑制CRC细胞活力和侵袭，并且在体内抑制CRC异种移植肿瘤生长。相反，在APCMin/+小鼠中阻断miR-194促进肿瘤生长。此外，miR-194在体外和体内均降低AKT 2的表达。临床上，miR-194的表达从20例正常结直肠黏膜（N-N）到40例结直肠腺瘤（CRA）再到40例CRC逐渐降低，并与AKT 2和pAKT 2表达呈负相关。此外，从20例健康人、20例CRA、28例CRC患者粪便标本中miR-194的表达逐渐降低。miR-194在结直肠癌组织中的低表达与肿瘤体积大（P=0.006）、淋巴结转移（P=0.012）和生存期短相关（HR =2.349，95%CI = 1.242 ~ 4.442; P=0.009）。结论：miR-194通过靶向PDK 1/AKT 2/XIAP通路在结直肠癌的发生发展中发挥抑癌作用，可能成为结直肠癌诊断和预后的重要生物标志物。
Abstract: Recent studies have increasingly linked microRNAs to colorectal cancer (CRC). MiR-194 has been reported deregulated in different tumor types, whereas the function of miR-194 in CRC largely remains unexplored. Here we investigated the biological effects, mechanisms and clinical significance of miR-194. Functional assay revealed that overexpression of miR-194 inhibited CRC cell viability and invasion in vitro and suppressed CRC xenograft tumor growth in vivo. Conversely, block of miR-194 in APCMin/+ mice promoted tumor growth. Furthermore, miR-194 reduced the expression of AKT2 both in vitro and in vivo. Clinically, the expression of miR-194 gradually decreased from 20 normal colorectal mucosa (N-N) cases through 40 colorectal adenomas (CRA) cases and then to 40 CRC cases, and was negatively correlated with AKT2 and pAKT2 expression. Furthermore, expression of miR-194 in stool samples was gradually decreased from 20 healthy cases, 20 CRA cases, then to 28 CRC cases. Low expression of miR-194 in CRC tissues was associated with large tumor size (P=0.006), lymph node metastasis (P=0.012) and shorter survival (HR =2.349, 95% CI = 1.242 to 4.442; P=0.009). In conclusion, our data indicated that miR-194 acted as a tumor suppressor in the colorectal carcinogenesis via targeting PDK1/AKT2/XIAP pathway, and could be a significant diagnostic and prognostic biomarker for CRC.
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