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下调的 HSA_circ_0003528 通过 miR-212-3p/轴抑制肝癌的侵袭能力。

Down-regulated HSA_circ_0003528 inhibits hepatocellular carcinoma aggressiveness via the miR-212-3p/ axis.

机构信息

Department of Gastroenterology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Department of Blood Transfusion, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

出版信息

Bioengineered. 2022 Apr;13(4):11269-11280. doi: 10.1080/21655979.2022.2066046.

Abstract

Hepatocellular carcinoma (HCC) is characterized by a high mortality rate. Dysregulated circular RNAs (circRNAs) play a vital role in HCC. We aimed to study the role of circ_0003528 in HCC and its fundamental molecular mechanisms. HSA_circ_0003528 was identified through bioinformatics dataset analysis. The binding sites between mRNA and miRNA were predicted using online bioinformatics tools. The interaction between miR-212-3p and X-linked inhibitor of apoptosis protein () or circ_0003528 was confirmed through the luciferase reporter assay. RT-qPCR and western blot assays were used to analyze the expression of all miRNAs/mRNAs and proteins. Cellular functions were evaluated using the MTT and TUNEL assays. A xenograft model was established to evaluate the function of circ_0003528 . Circ_0003528 was dramatically overexpressed in HepG2 and HUH7 cells. However, knockdown of circ_0003528 suppressed the aggressiveness of HCC cells and tumor growth both and . Furthermore, binding of miR-212-3p to circ_0003528 and was verified. Downregulation of miR-212-3p abrogated the effects of si-circ_0003528 on cell viability and apoptosis, and upregulation of antagonized the functions of the miR-212-3p mimic in HCC cells. circ_0003528 contributes to the development of HCC and via the miR-212-3p/ axis. Hence, circ_0003528 knockdown may be a potential therapeutic strategy for HCC treatment.

摘要

肝细胞癌(HCC)的死亡率很高。失调的环状 RNA(circRNA)在 HCC 中发挥着重要作用。我们旨在研究 circ_0003528 在 HCC 中的作用及其基本的分子机制。通过生物信息学数据集分析鉴定 HSA_circ_0003528。使用在线生物信息学工具预测 mRNA 和 miRNA 之间的结合位点。通过荧光素酶报告基因实验证实了 miR-212-3p 与 X 连锁凋亡抑制蛋白()或 circ_0003528 之间的相互作用。使用 RT-qPCR 和 Western blot 检测分析所有 miRNA/mRNAs 和蛋白的表达。通过 MTT 和 TUNEL 检测评估细胞功能。建立异种移植模型评估 circ_0003528 的功能。Circ_0003528 在 HepG2 和 HUH7 细胞中显著过表达。然而,circ_0003528 的敲低抑制了 HCC 细胞的侵袭性和肿瘤生长。此外,验证了 miR-212-3p 与 circ_0003528 和的结合。下调 miR-212-3p 消除了 si-circ_0003528 对细胞活力和凋亡的影响,而上调则拮抗了 miR-212-3p 模拟物在 HCC 细胞中的作用。Circ_0003528 通过 miR-212-3p/ 轴促进 HCC 的发展。因此,circ_0003528 的敲低可能是 HCC 治疗的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4773/9208529/ed76b8b78112/KBIE_A_2066046_UF0001_B.jpg

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