Abstract

Gastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro experiments demonstrated that circHAS2 knockdown or the addition of hsa-miR-944 mimics inhibited the proliferation, migration, and invasion ability of GC cells and affected the epithelial-mesenchymal transition. In addition, hsa-miR-944 interacted with protein phosphatase, Mg2+/Mn2+-dependent 1E (PPM1E), and was found to be a target gene of circHAS2. The upregulation of PPM1E reversed the effects of circHAS2 knockout on GC cells. The circHAS2/hsa-miR-944/PPM1E axis may be involved in the progression of GC; thus, circHAS2 may be a potential biomarker and therapeutic target for GC.

Highlights

  • Gastric cancer (GC) is considered to be one of the most common gastrointestinal malignancies, and its mortality rate ranks third worldwide [1, 2]

  • CircHAS2 is upregulated in GC and is associated with GC progression To investigate the biological function of circRNAs in GC, we analyzed the differentially expressed circRNAs in three pairs of GC tissues and corresponding paracancerous tissues from GSE121445 data

  • QPCR was used to verify the differences in expression levels of these seven upregulated circRNAs in 20 pairs of GC tissues and their corresponding paracancerous tissues

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Summary

Introduction

Gastric cancer (GC) is considered to be one of the most common gastrointestinal malignancies, and its mortality rate ranks third worldwide [1, 2]. GC can be caused by many factors including Helicobacter pylori infection, precancerous lesions, diet, or genetic factors [3, 4]. It tends to spread through the lymph nodes to neighboring tissues or organs and produces more cancer cells in the bloodstream [5]. CircRNAs are widely distributed in eukaryotic cells, have long half-lives, and are expressed at tissue- and stagespecific levels [12]. They can be used as a biomarker and therapeutic target for many tumors. Ding et al [13] found that circ-DONSON promoted the progression of GC by activating the expression of SRY-box transcription factor four via recruitment of the nucleosome remodeling factor complex

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