Abstract
The pathogenesis of GC involves the complex networking of multiple signaling pathways; however, the detailed mechanisms of tumorigenesis of GC remains largely unknown. Therefore, it is necessary to explore novel diagnostic/prognostic biomarkers for GC. In this study, the levels of hsa_circRNA_100269 in gastric cancer (GC) samples and cells were examined, and its effects on the biological functions of GC cells were elucidated. The levels of hsa_circRNA_100269 in specimens/cell lines were examined using RT-qPCR. Cell models with hsa_circRNA_100269 overexpression or knockdown were generated using lentiviral vectors. Cell viability was determined by MTT assay; cell migratory/invasive activity was evaluated using wound healing/Transwell assay. Cell cycle arrest and apoptosis were assessed by flow cytometry; expression of associated markers involved in cell apoptosis, EMT and the PI3K/Akt signaling were determined by RT-qPCR/immunoblotting. In vivo study was also performed using hsa_circRNA_100269 knockout mice. Our findings revealed downregulation of hsa_circRNA_100269 in GC tissues compared to non-cancerous control. Additionally, the levels of PI3K were remarkably elevated in GC tissues, where hsa_circRNA_100269 and PI3K was negatively correlated. Moreover, the expression of hsa_circRNA_100269 was associated with histology grade and occurrence of metastasis in GC patients. In addition, hsa_circRNA_100269 was downregulated in GC cells compared to normal gastric epithelial cells. Overexpressed hsa_circRNA_100269 notably inhibited the proliferation, migration, invasion and EMT of GC cells, whereas cell cycle arrest at G0/G1 phase was promoted and cell apoptosis was enhanced. Moreover, the PI3K/Akt signaling was involved in hsa_circRNA_100269-regulated GC cell proliferation, migration, invasion, EMT and apoptosis. Knockdown of hsa_circRNA_100269 also remarkably induced tumor growth in mouse model. In summary, our findings indicated that the levels of hsa_circRNA_100269 were reduced in GC. Furthermore, hsa_circRNA_100269 could suppress the development of GC by inactivating the PI3K/Akt pathway. More importantly, hsa_circRNA_100269/PI3K/Akt axis may be a novel therapeutic candidate for GC treatment.
Highlights
Gastric cancer (GC) is a type of aggressive tumor and one leading cause of cancer-related mortality, and the global incidence of GC are rising [1]
The results of Cox regression revealed that tumor size, T stage, histology grade, metastasis and circrRNA_100269 expression were independent risk factors to predict the prognosis of GC patients (Table 2)
The results indicated that the effects caused by downregulated hsa_circRNA_100269 in GC cells were abolished by inactivation of the PI3K/ Akt signaling (Fig 7)
Summary
Gastric cancer (GC) is a type of aggressive tumor and one leading cause of cancer-related mortality, and the global incidence of GC are rising [1]. The pathogenesis of GC is complicate, and a previous report has revealed that the five-year survival rate of GC patients in China remains poor [~25–30%; 2]. Modern therapeutic strategies for GC are developed and endoscopic and surgical resection are widely used for GC patients, but the prognosis of GC is still poor. The therapeutic outcome of patients with GC is relevant to disease staging at diagnosis, and the mortality of patients with advanced GC remains high [~30–50%; 3–5]. The detailed mechanisms during the onset and development of GC are still unclear. It is urgent to identify putative prognostic biomarkers for GC
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.
