Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China.
Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
Int J Clin Oncol. 2022 Oct;27(10):1562-1569. doi: 10.1007/s10147-022-02210-z. Epub 2022 Jul 7.
Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer.
The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis.
Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p.
By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer.
环状 RNA（circRNAs）在癌症发生中发挥关键作用。然而，circRNAs 在胃癌中的作用在很大程度上尚不清楚。本研究旨在研究 hsa_circ_0006282 在胃癌中的可能作用。
首先通过实时定量逆转录聚合酶链反应检测胃癌细胞系、85 例胃炎组织和 103 对胃癌组织和非肿瘤组织中 hsa_circ_0006282 的水平。进一步使用 RNA 干扰和 hsa_circ_0006282 表达质粒来操纵胃癌中 hsa_circ_0006282 的表达。最后，通过实时细胞分析、流式细胞术、Transwell、细胞克隆测定和 Western blot 分析来分析 hsa_circ_0006282 的生物学效应。
hsa_circ_0006282 在胃癌细胞、胃炎组织和胃癌组织中表达下调。下调 hsa_circ_0006282 后，细胞增殖、细胞迁移和抗凋亡能力增强，而过表达 hsa_circ_0006282 则得到相反的结果。此外，Western blot 显示，敲低和上调 hsa_circ_0006282 后，蛋白激酶 B（AKT）和细胞周期蛋白依赖性激酶 2（CDK2）的蛋白水平显著增加和减少，而磷酸酶和张力蛋白同源物缺失的第十染色体（PTEN）则显著相反调节。最后，hsa_circ_0006282 通过竞争性结合 hsa-miR-136-5p 促进了 PTEN 的表达。
hsa_circ_0006282 通过与 hsa-miR-136-5p 竞争结合，调节 PTEN/AKT 信号通路，抑制胃癌的生长。
