Up-regulated miR-17 promotes cell proliferation, tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma
Up-regulated miR-17 promotes cell proliferation, tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma
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上调的 miR-17 通过靶向结直肠癌中的 RND3 抑癌基因促进细胞增殖、肿瘤生长和细胞周期进展
DOI：
10.1042/bj20111517
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发表时间：
2012-03-01
影响因子：
4.1
通讯作者：
Liu, Li
中科院分区：
文献类型：
--
作者：
Luo, Hesan;Zou, Jinjin;Liu, Li
新出现的证据表明，miR-17家族可能在人类癌症肿瘤发生中起因果作用，但其对CRC（结直肠癌）发生的具体影响仍知之甚少。在本研究中，我们通过miRNA（microRNA）微阵列分析CRC组织样本，发现miR-17家族的四个成员在CRC组织中的表达高于正常组织。这一发现通过qRT-PCR（定量逆转录PCR）进一步验证。用miR-17的抑制剂转染CRC细胞降低了它们的增殖能力并诱导G（o）/G（1）停滞。我们还证实了miR-17在体外通过直接靶向RND 3发挥这一功能，并且在CRC组织和CRC细胞中miR-17的表达与RND 3的表达呈负相关。此外，在裸鼠异种移植模型中，miR-17抑制导致肿瘤生长抑制和RND 3表达上调。发现RND 3在CRC组织中的表达显著低于正常组织和腺瘤，表明RND 3可能在CRC中充当肿瘤抑制基因。总之，本研究表明，miR-17通过靶向RND 3在CRC癌变过程中发挥重要作用，并可能成为CRC的治疗剂。
Emerging evidence indicates that the miR-17 family may have a causal role in human cancer tumorigenesis, but their specific effects on the occurrence of CRC (colorectal carcinoma) are still poorly understood. In the present study, we profiled CRC tissue samples by miRNA (microRNA) microarray and found that four members of the miR-17 family had higher expression in CRC tissues than in normal tissues. This finding was further validated by qRT-PCR (quantitative reverse transcription PCR). Transfecting CRC cells with an inhibitor of miR-17 lowered their ability to proliferate and induced G(o)/G(1) arrest. We also confirmed that miR-17 exerted this function by directly targeting RND3 in vitro, and that the expression of miR-17 was negatively correlated with that of RND3 in CRC tissues and CRC cells. Moreover, miR-17 inhibition led to tumour growth suppression and up-regulation of RND3 expression in a nude mouse xenograft model. RND3 expression was found to be significantly lower in CRC tissues than in normal tissues and adenomas, indicating that RND3 may act as a tumour suppressor gene in CRC. In conclusion, the present study suggests that miR-17 plays an important role in CRC carcinogenesis by targeting RND3 and may be a therapeutic agent for CRC.