Abstract

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.

Highlights

  • Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer mortality worldwide [1]

  • MiR-214 is downregulated in gastric carcinoma tissues and four GC cell lines, compared with nontumourous gastric mucosa

  • Emerging evidence has highlighted the crucial impact of miRNA dysregulation on tumourigenesis of human carcinomas [3,4]

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Summary

Introduction

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer mortality worldwide [1]. Apart from conventional genetic and epigenetic alteration of protein-coding oncogenes and tumour-suppressor genes in the carcinogenesis of GC, nonprotein-coding RNAs, especially microRNAs (miRNAs), have emerged as a new player to shed light on the mechanism of GC development [2]. MiRNAs are endogenous 19–25 nt noncoding RNAs that negatively regulate protein expression by promoting mRNA degradation or repressing protein translation, through interaction with the 39-UTR of target mRNAs. A growing number of miRNAs have been reported to participate in carcinogenesis and development of human cancers, including GC [2,3,4]. A growing number of miRNAs have been reported to participate in carcinogenesis and development of human cancers, including GC [2,3,4] These miRNAs are usually dysregulated and function either as tumour suppressors or oncogenes in the initiation and progression of human carcinomas. We have found that miR-145 was downregulated in manifold human cancer cells and suppressed the invasionmetastasis cascade in GC by inhibiting N-cadherin protein translation [9,10]

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