miR-517a is an independent prognostic marker and contributes to cell migration and invasion in human colorectal cancer
miR-517a is an independent prognostic marker and contributes to cell migration and invasion in human colorectal cancer
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DOI：
10.3892/ol.2016.4269
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发表时间：
2016-04-01
期刊：
影响因子：
2.9
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
--
作者：
Ma, Wenqi;Yu, Qiang;Zhou, Qi
结直肠癌（CRC）是一种高度侵袭性肿瘤，经常伴有远处转移，这是预后不良的主要原因。然而，人们对转移机制仍知之甚少。 MicroRNA (miRNA/miR) 被认为与 CRC 进展有关。特别是，miR-517a被认为是一种新型的肿瘤相关miRNA，在肿瘤转移中具有潜在作用。采用逆转录定量聚合酶链反应检测CRC标本中miR-517a的表达。进行 Transwell 测定以确定 CRC 细胞的迁移和侵袭。使用公开数据库和蛋白质印迹分析公开了 miR-517a 的推定靶基因。本研究发现，与邻近的非肿瘤组织相比，CRC 组织中 miR-517a 的表达显着较高。临床分析表明，miR-517a 表达增加与 CRC 患者的不良预后特征和长期生存率相关。体外证据表明，miR-517a 的下调可抑制 HCT-116 细胞的细胞迁移和侵袭。相比之下，miR-517a 的上调增加了迁移和入侵的 SW480 细胞的数量。值得注意的是，CRC 细胞中 miR-517a 的表达受到叉头盒 J3 (FOXJ3) 丰度的反向调节。此外，在 CRC 组织中观察到 miR-517a 和 FOXJ3 表达之间呈负相关。总之，miR-517a似乎是预测CRC患者生存的独立预后标志物，并且可能通过抑制FOXJ3来促进细胞迁移和侵袭。
Colorectal cancer (CRC) is a highly invasive tumor that is frequently associated with distant metastasis, which is the primary cause of poor prognosis. However, the mechanisms of metastasis remain poorly understood. MicroRNAs (miRNAs/miRs) have been considered to be implicated in CRC progression. In particular, miR-517a is proposed as a novel tumor-associated miRNA and has a potential role in tumor metastasis. The expression of miR-517a in CRC specimens was detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were performed to determine the migration and invasion of CRC cells. The putative target genes of miR-517a were disclosed using publicly available databases and western blot analysis. The present study identified that the expression of miR-517a was significantly higher in CRC tissues as compared with adjacent non-tumor tissues. Clinical analysis indicated that increased expression of miR-517a was correlated with poor prognostic features and poor long-term survival of CRC patients. In vitro evidences demonstrated that downregulation of miR-517a inhibited cell migration and invasion in HCT-116 cells. By contrast, upregulation of miR-517a increased the number of migrated and invaded SW480 cells. Notably, miR-517a expression was inversely regulated by forkhead box J3 (FOXJ3) abundance in CRC cells. Furthermore, an inverse correlation between miR-517a and FOXJ3 expression was observed in CRC tissues. In conclusion, miR-517a appears to be an independent prognostic marker for predicting survival of CRC patients, and may promote cell migration and invasion by inhibiting FOXJ3.