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环状 RNA circ-ITCH 通过靶向 miR-145/RASA1 信号通路抑制卵巢癌进展。

The circular RNA circ-ITCH suppresses ovarian carcinoma progression through targeting miR-145/RASA1 signaling.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Gynecology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Gynecology, Changzhou Maternal and Child Health Care Hospital, Affiliated of Nanjing Medical University, Changzhou, China.

出版信息

Biochem Biophys Res Commun. 2018 Oct 20;505(1):222-228. doi: 10.1016/j.bbrc.2018.09.060. Epub 2018 Sep 19.

Abstract

As the leading cause of death for gynecological cancers, ovarian cancer (OC) ranks fifth overall for cancer-related death among women. Emerging evidence has indicated that circular RNA (circRNA), recognized as functional non-coding transcripts in eukaryotic cells, may be involved in many physiological or pathological processes. It was reported that circ-ITCH is downregulated in multi cancers and serves as a powerful tumor suppressor among through a competing endogenous RNA (ceRNA) pathway. However, the existence and the role of circ-ITCH in OC was not reported. Here, we found a broad down-regulation of circ-ITCH in OC tissues and cells, which correlates with a worse prognosis in OC patients. Functional studies suggest that circ-ITCH overexpression inhibits the cell viability and motility by CCK8, cell cycle, wound healing assay and invasion assay. It also inhibits the tumorigenesis ability in xenograft NOD mice in vivo. Mechanically, we demonstrated that circ-TCH acts as a ceRNA to sponge miR-145, increases the level of RASA1, and inhibits the malignant progression of OC cells via the circ-ITCH-miR-145-RASA1 axis in vitro and in vivo. Taken together, our findings provide a novel tumor suppressive role regarding circ-ITCH function in the malignant progression of OC.

摘要

作为妇科癌症的主要死亡原因,卵巢癌 (OC) 在女性癌症相关死亡中总体排名第五。新出现的证据表明,环状 RNA (circRNA) 作为真核细胞中的功能性非编码转录物,可能参与许多生理或病理过程。有报道称,circ-ITCH 在多种癌症中下调,并且通过竞争性内源性 RNA (ceRNA) 途径作为强大的肿瘤抑制因子发挥作用。然而,circ-ITCH 在 OC 中的存在和作用尚未报道。在这里,我们发现 OC 组织和细胞中 circ-ITCH 广泛下调,与 OC 患者的预后不良相关。功能研究表明,circ-ITCH 过表达通过 CCK8、细胞周期、划痕愈合实验和侵袭实验抑制细胞活力和迁移。它还抑制了体内异种移植 NOD 小鼠中的肿瘤发生能力。从机制上讲,我们证明 circ-TCH 作为 ceRNA 来海绵 miR-145,增加 RASA1 的水平,并通过 circ-ITCH-miR-145-RASA1 轴在体外和体内抑制 OC 细胞的恶性进展。综上所述,我们的研究结果提供了关于 circ-ITCH 在 OC 恶性进展中的肿瘤抑制作用的新见解。

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