Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs implicated in cancer progression. This study explored the expression levels, clinical implication and possible molecular mechanism of circRNA_102231 in gastric cancer (GC). Gene Expression Omnibus (GEO) was used to analyze differentially expressed circRNAs. CircRNA_102231 expression was verified by qRT-PCR in GC tissues and plasma. The effects of circRNA_102231 was tested by CCK-8, colony formation, EdU and Transwell assays and xenograft tumor model. RNA pull-down and immunoprecipitation (RIP) assays were used to analyze the interaction between circRNA_102231 and IRTKS. CircRNA_102231 expression was significantly upregulated in GC tissue and plasma samples, which can be used as a biomarker for GC diagnosis and prognosis. The function assays showed that circRNA_102231 knockdown inhibited GC cell proliferation and invasion both in vitro and in vivo. CircRNA_102231 was able to bind to IRTKS, increasing IRTKS protein stability, leading to GC progression. Overexpression of IRTKS effectively rescued the reduced cell viability and invasion caused by silencing of circRNA_102231. In sum, our data demonstrate that circRNA_102231 is a novel oncogene in GC and acts as a potential biomarker and therapeutic target for GC patients.

ObjectiveAngiogenesis is a critical step of breast cancer metastasis. Oncogenic Ras promotes the remodeling of cancer microenviroment. Tumor-associated macrophages (TAMs) are a prominent inflammatory cell population emerging in the microenviroment and facilitating the angiogenesis and metastasis. In the present study, we tried to investigate the relationship between the expression of Ras and infiltration of TAM, both of which could further promote angiogenesis.MethodsExpressions of Ras, CD68 and CD34 were assessed by immunohistochemistry. The infiltration of macrophages was evaluated by counting the number of CD68+ cells. Vessel endothelial cells were defined as CD34+ cells. Angiogenesis vascularity was defined by microvessel density (MVD) assay through counting the number of vessels per field counted in the area of highest vascular density. The Kaplan–Meier survival analysis was used to estimate the overall survival (OS). Macrophages were derived from monocytes in the presence of macrophage colony-stimulating-factor (MCSF). Breast cancer cells were treated with macrophage-conditioned medium (MCM) and tested the expressions of K-, H- and N-Ras by using realtime-PCR.ResultsRas positive status was correlated with ER, PR and Her-2 positivity, larger tumour size and lymph node metastasis, as well as higher TNM stages. A higher number of CD68+ cells was correlated with larger tumour size, higher TNM stages and Her-2 positivity. Both Ras positivity and infiltration of CD68+ macrophages correlated with poor OS. The number of CD68+ cells was positively correlated with the expression of Ras. Treatment with MCM did not up-regulate but repressed the expression of Ras. Both up-regulation of Ras and infiltration of TAMs correlated with increased MVD.ConclusionExpression of Ras and infiltration of TAM were positively correlated, and both participated in angiogenesis. Elevated Ras could be responsible for the infiltration of TAM.