Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
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DOI：
10.1002/mog2.39
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发表时间：
2023-06
期刊：
影响因子：
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通讯作者：
Yixun Lu;Guo-xiao Liu;Yanjun Wang;Kai Li;Xinxin Xu;Benlong Zhang;Lin Chen;H. Xi;Xinxin Wang
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文献类型：
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作者：
Yixun Lu;Guo-xiao Liu;Yanjun Wang;Kai Li;Xinxin Xu;Benlong Zhang;Lin Chen;H. Xi;Xinxin Wang
胃癌是世界范围内最常见的恶性肿瘤之一。令人信服的证据表明，环状RNA（circRNA）在多种癌症中起着关键作用。然而，circRNA在GC中的作用和机制仍不清楚。在这里，我们首先通过人circRNA微阵列鉴定了GC中显著过表达的环状RNA hsa_circ_0025506，命名为circGPRC 5A（e2）。接下来，我们发现circGPRC 5A（e2）在GC细胞系和临床样品中也过表达。然后，我们通过荧光原位杂交证实了circGPRC 5A（e2）主要定位于GC细胞的胞浆中，并观察到与miR-665的共定位现象。在功能上，Cell Counting Kit-8，5-Ethynyl-2′-deoxyuridine，克隆形成试验，Transwell侵袭试验，伤口愈合试验和动物实验表明，circGPRC 5A（e2）在体外促进GC增殖，迁移和侵袭，在体内促进肿瘤发生和转移。从机制上讲，我们发现circGPRC 5A（e2）可以作为miR-665海绵，通过调节miR-665/LIM和SH 3蛋白1（LASP 1）轴和激活磷脂酰肌醇3-激酶/AKT通路促进GC生长和转移。综上所述，这项研究揭示了circGPRC 5A（e2）在GC中作为癌基因发挥作用。目前研究揭示的circGPRC 5A（e2）/miR-665/LASP 1轴可能为GC提供新的生物标志物和有希望的治疗靶点。
Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overexpressed circular RNA hsa_circ_0025506 in GC by human circRNA microarray, designated as circGPRC5A(e2). Next, we found circGPRC5A(e2) was overexpressed in GC cell lines and clinical samples as well. Then, we confirmed that circGPRC5A(e2) was primarily located in the cytoplasm of GC cells and colocation phenomenon was observed with miR‐665 via fluorescence in situ hybridization. Functionally, Cell Counting Kit‐8, 5‐Ethynyl‐2′‐deoxyuridine, clone formation assay, Transwell invasion assay, wound‐healing assay, and animal experiments showed that circGPRC5A(e2) promoted GC proliferation, migration, and invasion in vitro, and tumorigenesis and metastasis in vivo. Mechanistically, we showed that circGPRC5A(e2) could serve as miR‐665 sponges and facilitate GC growth and metastasis via modulating miR‐665/LIM and SH3 protein 1 (LASP1) axis and activating phosphatidylinositol 3‐kinase/AKT pathway. Taken together, this study revealed that circGPRC5A(e2) functioned as an oncogene in GC. The circGPRC5A(e2)/miR‐665/LASP1 axis revealed by current research might provide novel biomarkers and promising therapeutic targets for GC.