Department of Hepatobiliary & Vascular Surgery, 580504School of Clinical Medicine & The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Operation Room, 580504School of Clinical Medicine & The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221115400. doi: 10.1177/09603271221115400.
Hsa_circ_0000285, a novel circular RNA, has been proven to extensively take part in the pathogenesis of numerous tumors. In hepatocellular carcinoma (HCC), very little is known about hsa_circ_0000285 until now. Hence, this research aims to determine hsa_circ_0000285's functional role and underlying mechanisms in HCC.
The expressions of miR-582-3p, hsa_circ_000028, and cyclin B2 (CCNB2) among the HCC cells and tumor samples were determined by performing western blotting and qRT-PCR analyses. The impacts of hsa_circ_000028 on the proliferative and migratory abilities of HCC cells were examined through the execution of CCK-8 and wound-healing assays. Meanwhile, the expressions of the proteins Bcl-2 and Bax were detected via western blotting. Tumor xenograft models were established to examine how hsa_circ_000028 functions during the mediation of HCC tumor growth in vivo. RNA immunoprecipitation and luciferase reporter experiments were performed for the validation of the interactions of miR-582-3p, hsa_circ_000028, and CCNB2 with each other.
Elevated hsa_circ_0000285 and CCNB2 expressions, and a decreased miR-582-3p expression were observed among the HCC cell lines and tumors. Hsa_circ_0000285 bound to miR-582-3p competitively to improve CCNB2 levels. Silencing of hsa_circ_0000285 promoted apoptosis and repressed proliferation and migration among HCC cells. Moreover, silencing hsa_circ_0000285 also impeded the growth of HCC tumors in vivo. Inhibiting hsa_circ_0000285 or CCNB2 reversed the miR-582-3p-knockdown-mediated promotion of malignant HCC cell phenotypes.
Our study has demonstrated that hsa_circ_0000285 fosters the development of malignant HCC cells phenotypes through the modulation of the miR-582-3p/CCNB2 axis. Thus, these results suggest that hsa_circ_0000285 is a prospective target for HCC treatment.
hsa_circ_0000285 是一种新型环状 RNA，已被证实广泛参与多种肿瘤的发病机制。在肝细胞癌 (HCC) 中，目前对 hsa_circ_0000285 知之甚少。因此，本研究旨在确定 hsa_circ_0000285 在 HCC 中的功能作用和潜在机制。
通过 Western blot 和 qRT-PCR 分析检测 HCC 细胞和肿瘤样本中 miR-582-3p、hsa_circ_000028 和 cyclin B2 (CCNB2) 的表达。通过 CCK-8 和划痕愈合实验检测 hsa_circ_000028 对 HCC 细胞增殖和迁移能力的影响。同时，通过 Western blot 检测 Bcl-2 和 Bax 蛋白的表达。建立肿瘤异种移植模型，检测 hsa_circ_000028 在体内介导 HCC 肿瘤生长过程中的作用。通过 RNA 免疫沉淀和荧光素酶报告实验验证 miR-582-3p、hsa_circ_000028 和 CCNB2 之间的相互作用。
在 HCC 细胞系和肿瘤中观察到 hsa_circ_0000285 升高和 CCNB2 表达升高，miR-582-3p 表达降低。hsa_circ_0000285 与 miR-582-3p 竞争结合以提高 CCNB2 水平。沉默 hsa_circ_0000285 促进 HCC 细胞凋亡，抑制增殖和迁移。此外，沉默 hsa_circ_0000285 还抑制 HCC 肿瘤在体内的生长。抑制 hsa_circ_0000285 或 CCNB2 逆转了 miR-582-3p 敲低介导的恶性 HCC 细胞表型的促进作用。
本研究表明，hsa_circ_0000285 通过调节 miR-582-3p/CCNB2 轴促进恶性 HCC 细胞表型的发展。因此，这些结果表明 hsa_circ_0000285 是 HCC 治疗的一个有前景的靶点。
