Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China.
Bioengineered. 2021 Dec;12(1):8279-8295. doi: 10.1080/21655979.2021.1984002.
Hsa_circ_0054537 (circ_0054537) is a novel tumor-related circular RNA in renal cell carcinoma (RCC), and we intended to ascertain its dysregulation and functions in RCC malignant progression, as well as the underlying mechanism via serving as competing endogenous RNA (ceRNA). In this research, using real-time quantitative PCR, we found circ_0054537 was upregulated in RCC tissues and cells, and distributed throughout the cytoplasm. Then, functional effects of circ_0054537 in RCC were detected using cell counting kit-8, transwell, flow cytometry and glycolysis stress test and adenosine Triphosphate (ATP) assays. The results uncovered that circ_0054537 knockdown inhibited cell proliferation, migration, invasion, autophagy and glycolysis, but promoted apoptosis in RCC cells. Notably, circ_0054537 was identified as a ceRNA for microRNA (miR)-640, and miR-640 could target neuronal pentraxin-2 (NPTX2), as evidenced by dual-luciferase reporter assay and RNA immunoprecipitation assay. Besides, miR-640 downregulation or NPTX2 overexpression partly overturned the tumor suppressor function of circ_0054537 silence and miR-640 overexpression in RCC cells. Additionally, RCC cell growth was retarded by circ_0054537 silence. In conclusion, circ_0054537/miR-640/NPTX2 ceRNA pathway regulated RCC malignant progression and curbed RCC tumor growth , which could be a potential diagnosis and therapeutic target of RCC.
Hsa_circ_0054537（circ_0054537）是肾细胞癌（RCC）中一种新型的肿瘤相关环状 RNA，我们旨在确定其在 RCC 恶性进展中的失调和功能，以及作为竞争性内源性 RNA（ceRNA）的潜在机制。在这项研究中，我们使用实时定量 PCR 发现 circ_0054537 在 RCC 组织和细胞中上调，并分布在细胞质中。然后，通过细胞计数试剂盒-8、Transwell、流式细胞术和糖酵解应激试验以及三磷酸腺苷（ATP）测定检测 circ_0054537 在 RCC 中的功能影响。结果表明，circ_0054537 敲低抑制了 RCC 细胞的增殖、迁移、侵袭、自噬和糖酵解，但促进了细胞凋亡。值得注意的是，circ_0054537 被鉴定为 microRNA（miR）-640 的 ceRNA，miR-640 可以靶向神经元五联蛋白-2（NPTX2），这一点得到了双荧光素酶报告基因检测和 RNA 免疫沉淀检测的证实。此外，miR-640 的下调或 NPTX2 的过表达部分逆转了 circ_0054537 沉默和 miR-640 过表达在 RCC 细胞中的肿瘤抑制功能。此外，circ_0054537 沉默抑制了 RCC 细胞的生长。总之，circ_0054537/miR-640/NPTX2 ceRNA 通路调节了 RCC 的恶性进展，并抑制了 RCC 肿瘤的生长，这可能是 RCC 的潜在诊断和治疗靶点。
