Abstract

ObjectivesGastric cancer (GC) is one of the most common malignant tumors. More and more evidences support the role of microRNAs (miRNAs) in tumor progression. However, the role of miRNAs in human GC remains largely unknown.MethodsBased on the published gastric cancer expression profile data, combined with bioinformatics analysis, potential miRNAs in the process of GC were screened. The expression of miR-199b-5p in GC cells and patients’ plasma was detected by RT-PCR. The effects of miR-199b-5p on GC in vitro were detected by EdU proliferation assay, colony formation assay, Transwell assay and wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) related proteins. The subcutaneous tumorigenesis model and metastatic tumor model of mice were used to study its effect in vivo. Bioinformatics and Dual luciferase reporter assay were used to verify the effect of miR-199b-5p and its target gene.ResultsThrough bioinformatics analysis, we screened a novel miRNA miR-199b-5p that was significantly up-regulated in GC tissue and associated with poor prognosis of GC patients. RT-PCR results showed that its expression was also up-regulated in GC cell lines and patients’ plasma. MiR-199b-5p can significantly promote GC cell proliferation and migration in vitro and in vivo. Western blot showed that miR-199b-5p could promote the EMT process of GC. HHIP has been proved to be a target of miR-199b-5p, and the recovery of HHIP can weaken the effect of miR-199b-5p.ConclusionMiR-199b-5p may play an oncogene role in GC by targeting HHIP, suggesting that miR-199b-5p may be a potential therapeutic target for GC.

Highlights

  • The incidence of gastric cancer (GC) has declined in the past few decades, it is still one of the most common malignant tumors, especially in East Asia, where its incidence and mortality rank fourth and third in the world, respectively [1, 2]

  • We found that miR-199b-5p is significantly highly expressed in gastric cancer tissues, and the highly expressed miR-199b is related to the poor prognosis of gastric cancer patients

  • Overexpression of HHIP can partially reverse the role of miR-199b-5p in GC, that is, the related role of miR-199b-5p in GC was partly caused by regulating HHIP. These findings provided a basis for miR-199b-5p as a potential therapeutic target for GC

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Summary

Introduction

The incidence of gastric cancer (GC) has declined in the past few decades, it is still one of the most common malignant tumors, especially in East Asia, where its incidence and mortality rank fourth and third in the world, respectively [1, 2]. MiRNA is a type of non-coding RNA composed of 20-24 nucleotides, which plays an important role in human health and disease by regulating gene expression [5, 6]. Mature miRNAs can play a bidirectional regulatory function by degrading or inhibiting the translation of target mRNAs, that is, miRNAs assume at least two functions of oncogene or tumor suppressor gene in life activities. MiR-199b-5p is under-expressed in prostate cancer and breast cancer and inhibits tumor cell growth [11, 12]. These studies show that miR-199b-5p plays a two-way regulatory role in different cancer cells. We found that miR-199b-5p can promote the progress of GC both in vivo and in vitro

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