School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province 523808, P.R. China.
Department of Chemotherapy, The People's Hospital of GaoZhou, GaoZhou, Guangdong Province 523808, P.R. China.
J Cell Biochem. 2018 Jan;119(1):440-446. doi: 10.1002/jcb.26201. Epub 2017 Jul 7.
Gastric cancer (GC) has one of the highest mortality rates of malignancies globally. Currently, ciRS-7, a novel circular RNA, has emerged as a potential sponge for miR-7. However, few studies on ciRS-7 in GC have been performed. In this study, we investigated the clinical significance and function of ciRS-7 in GC. First, the expression levels of ciRS-7 in 102 primary GC tissues and the matched para-carcinoma tissues were evaluated and the clinical relevance was confirmed in an independent validation cohort (n = 154). Second, the effects of ciRS-7 on miR-7, PTEN, and PI3K were evaluated. Finally, the function of ciRS-7 in GC was analyzed with cell lines and nude mice. The expression of ciRS-7 was significantly upregulated in GC tissues compared with the matched para-carcinoma tissues (P = 0.0023), and the upregulation of ciRS-7 was linked to poor survival in the testing (P = 0.0143) and validation cohort (P = 0.0061). Multivariate survival analysis revealed that ciRS-7 was probably an independent risk factor of overall survival (P < 0.05). Furthermore, overexpression of ciRS-7 blocked the miR-7-induced tumor suppression in MGC-803 and HGC-27 cells and led to a more aggressive oncogenic phenotype, via antagonizing miR-7-mediated PTEN/PI3K/AKT pathway. ciRS-7 may act as a prospective prognostic biological marker and a promising therapeutic target for GC. J. Cell. Biochem. 119: 440-446, 2018. © 2017 Wiley Periodicals, Inc.
胃癌（GC）是全球死亡率最高的恶性肿瘤之一。目前，一种新型的环状 RNA ciRS-7 已成为 miR-7 的潜在海绵。然而，关于 GC 中 ciRS-7 的研究很少。在本研究中，我们研究了 ciRS-7 在 GC 中的临床意义和功能。首先，评估了 102 例原发性 GC 组织和配对癌旁组织中 ciRS-7 的表达水平，并在独立验证队列（n=154）中证实了其临床相关性。其次，评估了 ciRS-7 对 miR-7、PTEN 和 PI3K 的影响。最后，通过细胞系和裸鼠分析了 ciRS-7 在 GC 中的功能。与配对癌旁组织相比，GC 组织中 ciRS-7 的表达明显上调（P=0.0023），ciRS-7 的上调与检测（P=0.0143）和验证队列（P=0.0061）中的不良生存相关。多变量生存分析表明 ciRS-7 可能是总生存的独立危险因素（P<0.05）。此外，ciRS-7 的过表达通过拮抗 miR-7 介导的 PTEN/PI3K/AKT 通路，阻断了 MGC-803 和 HGC-27 细胞中 miR-7 诱导的肿瘤抑制作用，并导致更具侵袭性的致癌表型。ciRS-7 可能是 GC 的一个有前途的预后生物标志物和治疗靶点。J. Cell. Biochem. 119: 440-446, 2018. © 2017 Wiley Periodicals, Inc.
