Compelling evidence indicates the regulatory role of circular RNAs in cancers, including hepatocellular carcinoma (HCC). Our study aimed to elucidate the regulatory function of circ_0129047 in HCC progression. A reverse transcription-quantitative polymeric chain reaction was conducted to detect the expression of circ_0129047, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1), and miR-492 in HCC tissues and cells. The characteristics of circ_0129047 were determined by evaluating the nuclear and cytoplasmic fractions and by RNase R digestion assays. The cell counting kit-8 assay, scratch wound, and transwell invasion assays were used to examine the effects of circ_0129047 overexpression, miR-492 mimic, and LYVE1 overexpression on the proliferation, migration, and invasion abilities of HCC cells in vitro. A mouse xenograft model was also established. The relationship between miR-492 and circ_0129047 or LYVE1 was clarified using luciferase reporter and Argonaute-2 RNA immunoprecipitation assays. We found that circ_0129047 and LYVE1 were poorly expressed in HCC tissues and cells, whereas miR-492 was upregulated. Overexpression of circ_0129047 inhibits HCC cell proliferation, migration, and invasion and delays in vivo tumor growth. Furthermore, circ_0129047 sponged miR-492, and 3′UTR LYVE1 was a direct target of miR-492. Additionally, LYVE1 overexpression reduced the oncogenic activity of the miR-492 mimic, whereas the miR-492 mimic abolished the antimigratory, antiproliferative, and anti-invasive effects of circ_0129047 overexpression in HCC cells. These data suggest that circ_0129047 exerts a tumor-suppressive role in HCC by sponging miR-492 away from LYVE1 and that the circ_0129047/miR-492/LYVE1 axis may be a promising target for HCC treatment.

中文翻译：

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hsa_circ_0129047 通过海绵 miR-492 上调 LYVE1 以抑制肝细胞癌进展

令人信服的证据表明环状 RNA 在癌症（包括肝细胞癌 (HCC)）中的调节作用。我们的研究旨在阐明 circ_0129047 在 HCC 进展中的调节功能。采用逆转录定量聚合链反应检测肝癌组织和细胞中circ_0129047、淋巴管内皮透明质酸受体-1（LYVE1）和miR-492的表达。circ_0129047 的特征是通过评估细胞核和细胞质部分以及 RNase R 消化测定来确定的。采用细胞计数试剂盒8法、划痕法和Transwell侵袭法检测circ_0129047过表达、miR-492模拟物和LYVE1过表达对体外HCC细胞增殖、迁移和侵袭能力的影响。还建立了小鼠异种移植模型。使用荧光素酶报告基因和 Argonaute-2 RNA 免疫沉淀测定阐明了 miR-492 和 circ_0129047 或 LYVE1 之间的关系。我们发现 circ_0129047 和 LYVE1 在 HCC 组织和细胞中表达较差，而 miR-492 表达上调。circ_0129047 的过度表达可抑制 HCC 细胞增殖、迁移和侵袭，并延迟体内肿瘤生长。此外，circ_0129047 海绵 miR-492，3'UTR LYVE1 是 miR-492 的直接靶标。此外，LYVE1 过表达降低了 miR-492 模拟物的致癌活性，而 miR-492 模拟物消除了 circ_0129047 过表达在 HCC 细胞中的抗迁移、抗增殖和抗侵袭作用。这些数据表明，circ_0129047 通过将 miR-492 远离 LYVE1 而在 HCC 中发挥肿瘤抑制作用，并且 circ_0129047/miR-492/LYVE1 轴可能是 HCC 治疗的一个有希望的靶点。