circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1.

Circular RNA (circRNA) participates in a variety of pathophysiological processes, including the development of gastric cancer (GC). However, the role of circ_0006089 in GC progression and its underlying molecular mechanism need to be further revealed. Quantitative real-time PCR was utilized for detecting circ_0006089, microRNA (miR)-361-3p and transforming growth factor-ß1 (TGFB1) expression. The interaction between miR-361-3p and circ_0006089 or TGFB1 was confirmed using a dual-luciferase reporter assay and an RNA immunoprecipitation (RIP) assay. Cell proliferation, metastasis, apoptosis, and angiogenesis were determined using colony formation assay, EdU assay, transwell assay, flow cytometry, and tube formation assay. Cell glycolysis was evaluated by detecting glucose consumption, lactate production, and ATP levels. In addition, western blot (WB) analysis was used to measure protein expression. Xenograft tumor models were used to assess the effect of circ_0006089 knockdown on GC tumorigenesis. circ_0006089 had been found to be upregulated in GC tissues and cells, and it could act as an miR-361-3p sponge. circ_0006089 knockdown suppressed GC proliferation, metastasis, glycolysis, angiogenesis, and increased apoptosis, while this effect could be revoked by miR-361-3p inhibitor. TGFB1 was targeted by miR-361-3p, and its overexpression reversed the effects of miR-361-3p on GC cell function. Also, circ_0006089 promoted TGFB1 expression via sponging miR-361-3p. Animal experiments showed that silenced circ_0006089 inhibited GC tumorigenesis through the miR-361-3p/TGFB1 pathway. Our results revealed that the circ_0006089/miR-361-3p/TGFB1 axis contributed to GC progression, confirming that circ_0006089 might be a potential therapeutic target for GC.

circ_0006089 facilitates gastric cancer progression and oxaliplatin resistance via miR-217/NRP1.

BACKGROUND: Oxaliplatin (OXA) is a vital tool in the chemotherapy of gastric cancer (GC) patients. Circular RNAs (circRNAs) are a group of non-coding RNAs that have been associated with tumorigenesis. Nevertheless, the function of circRNAs in OXA resistance of GC is unknown. METHODS: Circ_0006089/miR-217/NRP1 were elucidated through qRT-PCR in GC OXA-tolerant tissues and cell lines. OXA half-inhibitory concentration (IC50) was quantified by MTT assay. RNA pull-down and luciferase reporter tests were applied to characterize the interaction between circ_0006089 and miR-217, miR-217 and NRP1 in GC cells. RESULTS: The findings disclosed that circ_0006089 and NRP1 was heightened whereas miR-217 was dramatically declined in OXA-tolerant GC tissues and cell lines. OXA resistance was reduced and the proliferation, migration and invasion ability of OXA cells were diminished after silencing circ_0006089. In addition, circ_0006089 raised OXA resistance by sponging miR-217. Further studies revealed that miR-217 bound to NRP1 and weakened OXA resistance. In addition, it was found that circ_0006089 accelerated GC progression and OXA resistance by upregulating NRP1 expression via sponging miR-217. CONCLUSION: Circ_0006089 regulated OXA resistance in GC cells through miR-217/NRP1 axis, implying it was a promising biomarker for GC therapy.

circ_0006089 Facilitates Gastric Cancer Progression via Decoying miR- 515-5p and Up-regulating CXCL6.

BACKGROUND: Gastric cancer (GC) is the most common cancer globally. Recent research has suggested that circular RNAs (circRNAs) play crucial roles in GC tumorigenesis and progression. The present study is performed to clarify the possible mechanism of circRNA has_circ_0006089 (circ_0006089) in GC. METHODS: The differentially expressed circRNAs were screened out by analyzing the dataset GSE83- 521. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect circ_0006089, miR-515-5p and CXCL6 expression levels in GC tissues and cell lines. CCK-8, BrdU and Transwell assays were adopted to examine the biological function of circ_0006089 in GC cells. The interaction between miR-515-5p and circ_0006089, as well as between CXCL6 and miR-515-5p, was confirmed through bioinformatics, RNA immunoprecipitation (RIP) assay, dual-luciferase reporter gene assay and RNA pull-down assay. RESULTS: Circ_0006089 was significantly upregulated in GC tissues and cells, and miR-515-5p was remarkably downregulated. After knocking down circ_0006089 or overexpressing miR-515-5p, the growth, migration and invasion of GC cells were markedly reduced. In terms of mechanism, miR-515- 5p was verified to be the target of circ_0006089, and CXCL6 was validated as miR-515-5p's downstream target gene. Inhibiting miR-515-5p reversed the inhibitory effect knocking down circ_0006089 had on GC cell proliferation, migration and invasion. CONCLUSION: Circ_0006089 facilitates the malignant biological behaviors of GC cells via the miR-515- 5p/CXCL6 axis. Circ_0006089 can probably act as one of the important biomarkers and therapeutic targets in GC treatment strategies.

Circular RNA circ_0006089 promotes the progression of gastric cancer by regulating the miR-143-3p/PTBP3 axis and PI3K/AKT signaling pathway.

OBJECTIVES: Circular RNAs (circRNAs) play pivotal roles in malignancies including gastric cancer (GC). We aimed to investigate the biological function and regulatory mechanism of circ_0006089 in GC. METHODS: Circ_0006089, microRNA (miR)-143-3p, and polypyrimidine tract-binding protein 3 (PTBP3) expressions were measured via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in GC cell lines. Cell proliferative capacity was determined by colony formation and CCK-8 assays. Flow cytometry was employed for measuring cell apoptosis. Cell invasion and migration were measured via transwell and wound-healing assays. Western blot analysis was utilized for detecting protein expressions of E-cadherin, N-cadherin, vimentin, PTBP3, PI3K, p-PI3K, AKT, and p-AKT. Dual-reporter luciferase analysis was conducted to confirm the association between miR-143-3p and circ_0006089 or PTBP3. The role of circ_0006089 in vivo was detected via establishing a mice xenograft model. RESULTS: Circ_0006089 expression was increased in GC. Circ_0006089 downregulation suppressed the proliferation and metastasis and induced apoptosis of GC cells, which was counteracted by miR-143-3p inhibition or PTBP3 overexpression. In addition, circ_0006089 overexpression could promote GC progression. MiR-143-3p specially bound to circ_0006089 and PTBP3 was targeted by miR-143-3p. Moreover, circ_0006089 could regulate PTBP3 expression and the PI3K/AKT pathway by sponging miR-143-3p. Circ_0006089 knockdown also suppressed tumor growth. CONCLUSION: Circ_0006089 regulated miR-143-3p/PTBP3/PI3K/AKT pathway to facilitate GC progression.

Circular RNA circ_0006089 regulates the IGF1R expression by targeting miR-143-3p to promote gastric cancer proliferation, migration and invasion.

Circular RNAs (circRNAs) figure prominently in regulating the progression of a variety of human malignancies. This study was performed to probe how circ_0006089 functioned in gastric cancer (GC). CircRNA expression profile GSE83521 was downloaded from Gene Expression Omnibus (GEO) database, and circRNAs and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure circ_0006089, microRNA-143-3p (miR-143-3p) and insulin-like growth factor 1 receptor (IGF1R) mRNA expressions in GC tissues and cell lines. Kaplan-Meier curves were used to detect the relationship between circ_0006089 expression and overall survival time of GC patients. Cell counting kit-8 (CCK-8) and 5-bromo-2-deoxyuridine (BrdU) assays were employed to detect the proliferative ability of GC cells after circ_0006089 was overexpressed or knocked down. Wound healing assay and Transwell assay were executed to examine the migration and invasion ability of GC cells. Western blot was adopted to detect IGF1R protein expressions. Circ_0006089 expression was up-regulated in GC samples and cell lines. And high circ_0006089 expression was associated with shorter survival time in GC patients. Circ_0006089 overexpression in GC cells significantly accelerated GC cell proliferation, migration and invasion, whereas circ_0006089 knockdown resulted in the opposite effects. Additionally, miR-143-3p was validated as a downstream target of circ_0006089, and circ_0006089 could positively regulate IGF1R expression via repressing miR-143-3p. Circ_0006089 is highly expressed in GC, and it promotes the malignancy of GC cells via modulating miR-143-3p/IGF1R axis, suggesting that circ_0006089 may serve as a promising therapeutic target for GC.