MiR-1254 inhibits cell proliferation, migration, and invasion by down-regulating Smurf1 in gastric cancer

Mingkun Jiang,Yu He,Yugang Ge,Chao Yang,Hao Fan,Linling Lin,Li Yang,Yongchang Miao,Diancai Zhang,Liang Shi

doi:10.1038/s41419-018-1262-x

Abstract

Gastric cancer (GC) is one of the most frequent malignancies, and increasing evidence supports the contribution of microRNA (miRNAs) to cancer progression. miR-1254 has been confirmed to participate in the regulation of various cancers, while the function of miR-1254 in GC remains unknown. In this study, we investigated the role of miR-1254 in GC. The expression of miR-1254 was detected in human GC specimens and cell lines by miRNA RT-PCR. The effects of miR-1254 on GC proliferation were determined by CCK-8 proliferation assays, colony formation assays, 5-ethynyl-2′-deoxyuridine (EdU) incorporation, and cell-cycle assays. The ability of migration and invasion was examined by transwell and wound-healing assay. Dual Luciferase reporter assay was used to validate the interaction of miR-1254 with its target gene. The xenograft mouse models were conducted to investigate the effects of miR-1254 in vivo. The signaling pathways and epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot. The results showed that miR-1254 inhibited the proliferation, migration and invasion in vitro and suppressed tumorigenesis in vivo. Smurf1 was shown to be the direct target of miR-1254. Overexpressing Smurf1 could partially counteract the effects caused by miR-1254. Similarly, the effects of the miR-1254-inhibitor were also rescued by Smurf1-shRNA. Furthermore, we found that miR-1254 inhibited EMT and decreased the PI3K/AKT signaling pathway through downregulating Smurf1. In summary, overexpression of miR-1254 could suppress proliferation, migration, invasion, and EMT via PI3K/AKT signaling pathways by downregulation of Smurf1 in GC, which suggests a potential therapeutic target for GC.

Highlights

Gastric cancer (GC) is one of the most frequent malignancies, in Eastern Asia, its incidence and mortality rank the fourth and the third, respectively, in the world[1]
To confirm whether miR-1254 was abnormally regulated in GC tissues, 90 pairs of GC tissues and adjacent normal tissues were collected to examine the relative expression of miR-1254 by miRNA RT-PCR
We investigated the correlation between the miR-1254 expression and clinicopathologic features of GC

Summary

Introduction

Gastric cancer (GC) is one of the most frequent malignancies, in Eastern Asia, its incidence and mortality rank the fourth and the third, respectively, in the world[1]. MicroRNAs (miRNAs) are a class of evolutionary conserved, small noncoding RNAs consisting of 18–25 nucleotides, which downregulate target mRNAs expression by binding to the 3′-untranslated regions (3′-UTR), leading to suppression of translation or mRNAs degradation[4,5]. The first miRNA was discovered as a small RNA transcribed from the Caenorhabditis elegans lin-4 locus in Official journal of the Cell Death Differentiation Association. MiRNAs have been described as playing an important role in the progression of cancer, such as tumor proliferation, invasion, and metastasis[8]. Dysregulation of miRNAs expression promotes the development of cancer due to the activation of oncogenes and silence of tumor-suppressor genes[9,10]. We found that miR-1254 inhibited the progression of GC both in vitro and in vivo

Objectives

Methods

Results

Conclusion