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环状 RNA hsa_circ_0001368 通过调控 miR-6506-5p/FOXO3 轴抑制胃癌进展。

Circular RNA hsa_circ_0001368 suppresses the progression of gastric cancer by regulating miR-6506-5p/FOXO3 axis.

机构信息

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.

出版信息

Biochem Biophys Res Commun. 2019 Apr 23;512(1):29-33. doi: 10.1016/j.bbrc.2019.02.111. Epub 2019 Mar 7.

DOI:10.1016/j.bbrc.2019.02.111
PMID:30853185
Abstract

Gastric cancer (GC) is still a major aggressive malignancy worldwide. While the importance of circular RNAs (circRNAs) involved in carcinogenesis has gradually been acknowledged, their role in human cancers is not largely understood, including in GC. Here, we focused on hsa_circ_0001368 in GC, a novel circRNA that has not been previously reported. In the current study, we found a broad downregulation of hsa_circ_0001368 in GC tissues and cells, which correlates with a worse prognosis in GC patients. Functional experiments suggested that the knockdown of hsa_circ_0001368 promoted cell viability and motility by cell proliferation and invasion assays. In addition, the knockdown of hsa_circ_0001368 led to accelerated tumor growth in vivo. Mechanically, we demonstrated that hsa_circ_0001368 served as a competing endogenous RNA (ceRNA) to sponge miR-6506-5p. Subsequently, FOXO3 may act as the functional target of miR-6506-5p, and the knockdown of hsa_circ_0001368 decreased the expression of the tumor-suppressive gene FOXO3. Taken together, our study revealed that hsa_circ_0001368 plays a tumor-suppression role in GC via the miR-6506-5p/FOXO3 axis and may serve as a potential target for GC therapy.

摘要

胃癌(GC)仍然是全球主要的侵袭性恶性肿瘤。虽然涉及致癌作用的环状 RNA(circRNA)的重要性逐渐得到承认,但它们在人类癌症中的作用,包括在 GC 中的作用,尚未被广泛理解。在这里,我们专注于 hsa_circ_0001368 在 GC 中的作用,这是一种以前未报道过的新型 circRNA。在本研究中,我们发现 hsa_circ_0001368 在 GC 组织和细胞中广泛下调,与 GC 患者的预后较差相关。功能实验表明,hsa_circ_0001368 通过细胞增殖和侵袭实验促进细胞活力和迁移。此外,hsa_circ_0001368 的敲低导致体内肿瘤生长加速。从机制上讲,我们证明 hsa_circ_0001368 作为竞争性内源 RNA(ceRNA)来海绵 miR-6506-5p。随后,FOXO3 可能作为 miR-6506-5p 的功能靶标,而 hsa_circ_0001368 的敲低降低了肿瘤抑制基因 FOXO3 的表达。总之,我们的研究表明,hsa_circ_0001368 通过 miR-6506-5p/FOXO3 轴在 GC 中发挥肿瘤抑制作用,并可能作为 GC 治疗的潜在靶点。

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