Circular <scp>RNA</scp> circ_0006089 promotes the progression of gastric cancer by regulating the <scp>miR</scp> ‐143‐3p/ <scp> <i>PTBP3</i> </scp> axis and <scp>PI3K</scp> / <scp>AKT</scp> signaling pathway

PI3K/AKT/mTOR通路 蛋白激酶B 小RNA 细胞生长 细胞凋亡 下调和上调 基因敲除 分子生物学 波形蛋白 流式细胞术 癌症研究 化学 生物 免疫学 基因 免疫组织化学 生物化学
作者
Guangrong Lin,Weirong Chen,Peihong Zheng,Weishan Chen,Gaoyang Cai
出处
期刊:Journal of Digestive Diseases [Wiley]
卷期号:23 (7): 376-387
标识
DOI:10.1111/1751-2980.13116
摘要

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.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.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.Circ_0006089 regulated miR-143-3p/PTBP3/PI3K/AKT pathway to facilitate GC progression.
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