MicroRNA-378-5p suppresses cell proliferation and induces apoptosis in colorectal cancer cells by targeting BRAF.
MicroRNA-378-5p suppresses cell proliferation and induces apoptosis in colorectal cancer cells by targeting BRAF.
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DOI：
10.1186/s12935-015-0192-2
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发表时间：
2015
影响因子：
5.8
通讯作者：
Zhao R
中科院分区：
文献类型：
--
作者：
Wang Z;Ma B;Ji X;Deng Y;Zhang T;Zhang X;Gao H;Sun H;Wu H;Chen X;Zhao R
MicroRNAs （miRNAs）是一组小的非编码RNA分子，可能在肿瘤发生中发挥关键作用。越来越多的证据表明，miR-378-5p在包括结直肠癌（CRC）在内的许多人类癌症中失调，这推测miR-378-5p可能在肿瘤发生中发挥重要作用。然而，由于缺乏靶基因信息，其在结直肠癌癌变中的作用仍不明确。在本研究中，通过定量逆转录聚合酶链反应（qRT-PCR）证实了miR-378-5p在CRC组织和细胞系中的表达下调。此外，CCK-8实验表明，过表达miR-378-5p可抑制细胞增殖。流式细胞分析表明，过表达miR-378-5p可诱导CRC细胞周期阻滞并促进细胞凋亡。荧光素酶报告基因检测表明BRAF是miR-378-5p的直接靶点。Western blot和qRT-PCR分析显示，miR-378-5p在CRC细胞中显著下调BRAF。此外，与邻近非肿瘤组织相比，CRC组织中miR-378-5p与BRAF呈负相关。这些结果表明，下调miR-378-5p通过靶向BRAF促进结直肠癌细胞生长，恢复其水平是一种潜在的有前景的治疗结直肠癌的方法。
MicroRNAs (miRNAs) are a group of small non-coding RNA molecules that potentially play a critical role in tumorigenesis. Increasing evidences indicate that miR-378-5p is dysregulated in numerous human cancers including colorectal cancer (CRC) which hypothesizes that miR-378-5p may play an important role in tumorigenesis. However, its role in CRC carcinogenesis remains poorly defined because of lacking target genes information. In the present study, it was demonstrated that the expression of miR-378-5p was down-regulated in CRC tissues and cell lines as determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Furthermore, overexpression of miR-378-5p suppressed cell proliferation, as indicated by CCK-8 assay. Flow cytometric analysis demonstrated that overexpression of miR-378-5p induced cell cycle arrest and promoted apoptosis in CRC cells. A luciferase reporter assay indicated that BRAF was a direct target of miR-378-5p. Western blot and qRT-PCR analysis indicated that BRAF was significantly down-regulated by miR-378-5p in CRC cells. Moreover, miR-378-5p was negatively associated with BRAF in CRC tissues compared to adjacent non-tumor tissues. These results demonstrate that down-regulation of miR-378-5p promotes CRC cells growth by targeting BRAF and restoration of their levels is a potentially promising therapeutic in CRC.