Clinicopathological significance of microRNA-214 in gastric cancer and its effect on cell biological behaviour.
Clinicopathological significance of microRNA-214 in gastric cancer and its effect on cell biological behaviour.
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MicroRNA-214在胃癌中的临床病理意义及其对细胞生物学行为的影响
DOI：
10.1371/journal.pone.0091307
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gao P
中科院分区：
文献类型：
--
作者：
Wang YW;Shi DB;Chen X;Gao C;Gao P
越来越多的证据表明，多种microRNA参与了胃癌的发生和发展，但microRNA-214在胃癌中的临床意义尚不清楚，microRNA-214在胃癌中的确切作用尚不清楚。本研究采用逆转录-实时定量聚合酶链反应（RT-qPCR）技术检测80例胃癌组织、18例非肿瘤组织和4种胃癌细胞株中microRNA-214的表达水平，探讨microRNA-214表达与胃癌临床病理特征及预后的关系。为了研究microRNA-214在胃癌细胞生物学行为中的潜在作用，我们在体外对四种胃癌细胞系和一种永生化胃癌细胞系进行了细胞增殖、凋亡、迁移和侵袭试验。我们的研究结果表明，microRNA-214在胃癌组织和胃癌细胞系中显著下调，与非肿瘤胃组织相比。microRNA-214在正常胃粘膜、未转移胃癌组织和转移胃癌组织中表达呈阶梯性下调。microRNA-214的表达与淋巴结转移和肿瘤大小呈显著负相关，但与患者的预后无关。microRNA-214的异位表达可以抑制胃癌细胞SGC 7901和MKN 45的细胞迁移和侵袭能力。在MKN 28、BGC 823和GES-1细胞中，microRNA-214的敲低可显著促进细胞增殖、迁移和侵袭，且具有细胞特异性。集落刺激因子1（CSF 1）被鉴定为microRNA-214的靶基因。总之，我们的数据表明microRNA-214是胃癌患者淋巴结转移的一种有前途的新生物标志物。我们发现microRNA-214的下调可能通过直接靶向CSF 1来调节胃癌细胞的增殖、侵袭和迁移。
Accumulating evidence indicates that numerous microRNAs are involved in the tumorigenesis and progression of gastric cancer, while the clinical significance of microRNA-214 in gastric cancer is poorly understood and the exact role of microRNA-214 in gastric cancer remains obscure. In the present study, expression levels of microRNA-214 in 80 gastric carcinoma tissues, 18 nontumourous gastric tissues, and 4 types of gastric cancer cell lines were quantified by reverse transcription followed by real-time quantitative polymerase chain reaction (RT-qPCR), and the relationship between microRNA-214 expression and cliniopathological characteristics including prognosis was explored. To investigate the potential role of microRNA-214 in gastric cancer cell biological behaviour, we performed cell proliferation, apoptosis, migration and invasion assays in four gastric cancer cell lines and an immortalized gastric cell line in vitro. Our results showed that microRNA-214 was dramatically downregulated in gastric cancer tissues and gastric cancer cell lines, compared with nontumourous gastric tissues. Stepwise downregulation of microRNA-214 expression was observed among nontumourous gastric mucosa, nonmetastasis gastric cancer tissues, and metastasis gastric cancer tissues. The expression of microRNA-214 was significantly inversely correlated with lymph node metastasis and tumour size but had no correlation with the patient's prognosis. Ectopic expression of microRNA-214 could inhibit cell migration and invasion ability in SGC7901 and MKN45 gastric cancer cells. And knockdown of microRNA-214 significantly facilitated cell proliferation, migration and invasion in a cell-specific manner in MKN28, BGC823 and GES-1 cells. Colony stimulating factor 1 (CSF1) was identified as a target gene of microRNA-214. In summary, our data demonstrated that microRNA-214 is a promising novel biomarker for lymph node metastasis in patients with gastric cancer. And we identified that downregulation of microRNA-214 may regulate the proliferation, invasion and migration of gastric cancer cells by directly targeting CSF1.
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