Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Aging (Albany NY). 2020 Feb 12;12(3):2485-2497. doi: 10.18632/aging.102756.
Circular RNA (circRNA) remains a tumour-related factor in various biological cells and plays regulatory roles in gene expression. It is a type of non-coding RNA, whereas the function of human circRNA in hepatocellular carcinoma (HCC) is still not clear yet. Our investigation used the HCC cell line to uncover the biological function of hsa_circ_0056836 in the development and progression of hepatocellular carcinoma.
The present study showed that hsa_circ_0056836 revealed high expressions in HCC cell lines and tissues compared with corresponding controls. Silencing of Hsa_circ_0056836 decreased cell migration, proliferation and invasion. Silencing of hsa_circ_0056836 inhibited the development of HCC in xenograft nude mice. Mechanistically, we found that hsa_circ_0056836 directly bound to miR-766-3p, thereby alleviating the targeted inhibition of Fos-related antigen 2 (FOSL2). The results of this study indicated that hsa_circ_0056836 is a novel oncogenic RNA of vast potential as a tumor biomarker.
In summary, the hsa_circ_0056836 / miR-766-3p / FOSL2 axis may serve as a promising strategy for HCC treatment.
First, the expressions of hsa_circ_0056836 in HCC tissues and corresponding para-cancerous tissues as well as in HCC cell lines and normal hepatocytes THLE-3 were detected by RT-PCR. Subcellular localization of hsa_circ_0056836 was confirmed by FISH. To detect the association between hsa_circ_0056836 and miR-766-3p, AGO2-RIP and Luciferase reporter assay were adopted. Loss of function study was applied to assess the role of hsa_circ_0056836 in HCC and to determine tumorigenesis in nude mice.
环状 RNA（circRNA）是各种生物细胞中的一种肿瘤相关因子，在基因表达中发挥着调控作用。它是一种非编码 RNA，然而，人类 circRNA 在肝细胞癌（HCC）中的功能尚不清楚。我们的研究利用 HCC 细胞系揭示了 hsa_circ_0056836 在肝癌发生和发展中的生物学功能。
本研究表明，与相应对照相比，hsa_circ_0056836 在 HCC 细胞系和组织中表达较高。hsa_circ_0056836 的沉默降低了细胞迁移、增殖和侵袭。hsa_circ_0056836 的沉默抑制了异种移植裸鼠 HCC 的发展。机制上，我们发现 hsa_circ_0056836 直接与 miR-766-3p 结合，从而减轻了对 Fos 相关抗原 2（FOSL2）的靶向抑制。这项研究的结果表明，hsa_circ_0056836 是一种具有巨大潜力的新型致癌 RNA，可以作为肿瘤标志物。
总之，hsa_circ_0056836/miR-766-3p/FOSL2 轴可能成为 HCC 治疗的一种有前途的策略。
首先，通过 RT-PCR 检测 HCC 组织和相应癌旁组织以及 HCC 细胞系和正常肝细胞 THLE-3 中 hsa_circ_0056836 的表达。通过 FISH 证实 hsa_circ_0056836 的亚细胞定位。采用 AGO2-RIP 和荧光素酶报告基因检测法检测 hsa_circ_0056836 与 miR-766-3p 的相关性。采用功能丧失研究评估 hsa_circ_0056836 在 HCC 中的作用，并在裸鼠中确定肿瘤发生情况。
