Abstract
Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.
Highlights
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide [1]
Liu et al recently demonstrated that circDLC1 was downregulated in hepatocellular carcinoma (HCC) tissues and inhibits HCC progression via interaction with RNAbinding protein HuR [15]; Zhang et al previously found that an endogenous circRNA is decreased in glioblastoma and suppresses oncogenic transcriptional elongation through encoding peptides [16]
Hsa_circ_0110389 is up-regulated in gastric cancer (GC) tissues and cells, and high hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis RNA sequencing (RNA-seq) analysis between malignant-transformed human gastric epithelial cells (GES-1-T cells) induced by MNNG and negative control (NC) cells (GES1-N cells) was conducted in our previous study [17, 18], and the heat map expression results showed that hsa_circ_0110389, accession id according to the annotation of circBase, was highly up-regulated in gastric epithelial cells-1 (GES-1)-T cells (Fig. 1A)
Summary
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide [1]. The development of GC is considered to be a gradual process and a quantity of risk factors involve in GC etiology, among which environmental carcinogen exposure is one of the most common causes [5]; N-methyl-N′-nitro-Nnitrosoguanidine (MNNG) is a well-known environmental carcinogen that can result in the occurrence of cancers, especially GC [6]. Advances in high-throughput RNA sequencing (RNA-seq) technologies and novel bioinformatics algorithms have identified a growing number of circRNAs [8]. Studies have increasingly found that the dynamic expression patterns of circRNAs were involved in a variety of developmental stages, biological processes, and physiological conditions [9, 10]. Increasing studies have found that circRNAs are dysregulated in human cancers and play important roles in the occurrence and development of human cancers. In the context of GC, our previous studies have
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
