Abstract
ObjectivesCircular RNAs (circRNAs) are non‐coding RNAs, some of which are thought to be involved in gastric cancer development. Here, we examined the functions of circRNA hsa_circ_006100 in gastric cancer cells and an animal model of gastric cancer.Materials and MethodsThe expression of hsa_circ_006100, miR‐195 and various functional genes was determined by quantitative RT‐PCR. Cell viability, clone formation, apoptosis and cell migration/invasion abilities were analysed by the CCK‐8 assay, crystal violet staining, Hoechst staining and Transwell assay, respectively. A tumour model was established by subcutaneously injecting tumour cells into nude mice. Levels of protein expression were analysed by Western blotting and immunohistochemistry.ResultsA bioinformatics analysis showed that miR‐195 was negatively co‐expressed with hsa_circ_006100. Patients with a high hsa_circ_006100 level or low miR‐195 level had tumours with a high TNM stage, poor cellular differentiation and lymph node metastasis. miR‐195 was targeted and inhibited by hsa_circ_006100. Overexpression of hsa_circ_006100 enhanced cellular viability and proliferation, while miR‐195 suppressed hsa_circ_006100‐enhanced cell growth and induced apoptosis in MGC‐803 and AGS cells. Forced hsa_circ_006100 expression promoted the migration and invasion of MGC‐803 and AGS cells, while those activities were inhibited by miR‐195. Mechanistically, GPRC5A was predicted as a target of miR‐195 and was upregulated in gastric cancer. A miR‐195 inhibitor restored cell viability, proliferation, migration and invasion, and repressed apoptosis via GPRC5A. In vivo studies showed that knockdown of hsa_circ_006100 delayed tumour growth, reduced PCNA expression and upregulated miR‐195 and BCL‐2 expression which was restored by miR‐195 inhibition due to GPRC5A/EGFR signalling, and changed the EMT phenotype in vivo.ConclusionsHsa_circ_006100 functions as an oncogene in gastric cancer and exerts its effects via miR‐195/GPRC5A signalling.
Highlights
Gastric cancer (GC) is a common malignant tumour, and despite its declining incidence over the past century, it is a major cause of can‐ cer‐related death worldwide
We previously identified a series of ncRNAs involved in the N‐meth‐ yl‐N'‐nitro‐N‐nitrosoguanidine (MNNG)‐induced transformation of GES‐1‐T human gastric epithelial cells
One of those ncRNAs (LncRNA LOC101927497) functions as a tumour suppressor by in‐ teracting with miR‐574 to inhibit GC cell proliferation and migration, suggesting that ncRNAs might assist in regulating GC progression.[8]
Summary
Gastric cancer (GC) is a common malignant tumour, and despite its declining incidence over the past century, it is a major cause of can‐ cer‐related death worldwide. We previously identified a series of ncRNAs involved in the N‐meth‐ yl‐N'‐nitro‐N‐nitrosoguanidine (MNNG)‐induced transformation of GES‐1‐T human gastric epithelial cells. One of those ncRNAs (LncRNA LOC101927497) functions as a tumour suppressor by in‐ teracting with miR‐574 to inhibit GC cell proliferation and migration, suggesting that ncRNAs might assist in regulating GC progression.[8]. We screened the circRNAs‐miRNA network that is reported to exist during the transformation of human gastric epithelial cells and found that circRNA hsa_circ_006100 was signifi‐ cantly upregulated in cancerous cells, while miR‐195 expression was reduced. We found that circRNA hsa_circ_006100 functions as an oncogene to promote GC cell proliferation and metastasis via regulation of miR‐195 and its target gene GPRC5A
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