Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.
Int J Med Sci. 2020 May 18;17(9):1177-1186. doi: 10.7150/ijms.44550. eCollection 2020.
Circular RNA (circRNA), a member of non-coding RNA, plays an essential regulatory role in many human physiological and pathological processes; however, its role in clear cell renal cell carcinoma (ccRCC) still unclear. This study aims to investigate the effect and mechanisms of circRNA on ccRCC progression. A human circRNA microarray was used to discover differential expression circRNA, and a quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression of circRNA. The function and mechanism of circRNA were explored by cell transfection, cell counting kit-8, fluorescein isothiocyanate (FITC) Annexin V apoptosis detection, wound healing, transwell, and western blot. The result indicated that circ-APBB1IP was significantly up-regulated in ccRCC. In vitro, knockdown of circ-APBB1IP by siRNA suppressed the proliferation, migration, and invasion and increased the apoptosis of ccRCC cells. Further study found that knockdown of circ-APBB1IP up-regulated protein expression of cleaved caspase-3, cleaved caspase-7, cleaved caspase-8, cleaved caspase-9, Bax, Bad, Bak, E-cadherin and down-regulated expression of Bcl-2, N-cadherin, MMP-2, MMP-9, p-ERK1/2. Our result indicates that circ-APBB1IP has a vital function in ccRCC tumorigenesis. These findings suggest that circ-APBB1IP represents a novel potential biomarker and therapeutic target of ccRCC.
环状 RNA（circRNA）作为非编码 RNA 的一员，在许多人类生理和病理过程中发挥着重要的调节作用；然而，其在透明细胞肾细胞癌（ccRCC）中的作用尚不清楚。本研究旨在探讨 circRNA 对 ccRCC 进展的影响及其机制。采用人类 circRNA 微阵列发现差异表达的 circRNA，并用实时定量聚合酶链反应（qRT-PCR）验证 circRNA 的表达。通过细胞转染、细胞计数试剂盒-8（CCK-8）、荧光素异硫氰酸酯（FITC） Annexin V 凋亡检测、划痕愈合、Transwell 实验和 Western blot 探索 circRNA 的功能和机制。结果表明，circ-APBB1IP 在 ccRCC 中显著上调。在体外，通过 siRNA 敲低 circ-APBB1IP 抑制了 ccRCC 细胞的增殖、迁移和侵袭，并增加了细胞凋亡。进一步的研究发现，敲低 circ-APBB1IP 上调了 cleaved caspase-3、cleaved caspase-7、cleaved caspase-8、cleaved caspase-9、Bax、Bad、Bak、E-cadherin 的蛋白表达水平，下调了 Bcl-2、N-cadherin、MMP-2、MMP-9、p-ERK1/2 的表达水平。我们的结果表明，circ-APBB1IP 在 ccRCC 肿瘤发生中具有重要功能。这些发现表明，circ-APBB1IP 可能是 ccRCC 的一种新的潜在生物标志物和治疗靶点。
