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环状 RNA HOMER1 通过增强 miR-1322 对 CXCL6 的抑制作用来调节肝癌细胞的生长和侵袭。

Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells.

机构信息

Department of Vascular Surgery, Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

出版信息

J Cell Biochem. 2020 Nov;121(11):4440-4449. doi: 10.1002/jcb.29672. Epub 2020 Feb 9.

DOI:10.1002/jcb.29672
PMID:32037619
Abstract

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide accompanying with the high rate of recurrence. Accumulating reports have documented the significance of circular RNAs (circRNAs) in carcinogenesis and development of HCC. This study aimed to establish the mechanism underlying circ-HOMER1 involvement in HCC. To this end, we identified a binding site for miR-1322 via bioinformatics, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and dual-luciferase reporter assays providing evidence of a direct link between circ-HOMER1 and miR-1322. Similarly, the target gene of miR-1322 was investigated. Moreover, we determined the specific function of circ-HOMER1 in HCC with the aid of qRT-PCR based on patient clinical records, Cell Counting Kit-8, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, and wound-healing and transwell assays. Notably, circ-HOMER1 was upregulated in both HCC cells and tissues. This aberrant expression pattern was closely correlated with larger tumor size, higher tumor-node-metastasis stage, and poorer prognosis for the patients with HCC. Moreover, silenced circ-HOMER1 inhibited cell proliferation, migration, and invasion concomitant with the promotion of apoptosis in HCC cells, and vice versa. Mechanistically, circ-HOMER1 enhanced the inhibition of miR-1322 on CXCL6 in HCC. Furthermore, we found that circ-HOMER1 promoted HCC cell growth and aggressiveness by miR-1322/CXCL6 axis. This study may provide a potential prognostic indicator and therapeutic target for patients with HCC.

摘要

肝细胞癌 (HCC) 是一种常见的肝脏恶性肿瘤,在全球范围内伴有高复发率。越来越多的报道记录了环状 RNA (circRNA) 在 HCC 的发生和发展中的重要性。本研究旨在建立 circ-HOMER1 参与 HCC 的机制。为此,我们通过生物信息学、定量逆转录聚合酶链反应 (qRT-PCR) 和双荧光素酶报告基因检测鉴定了 miR-1322 的结合位点,为 circ-HOMER1 和 miR-1322 之间的直接联系提供了证据。同样,研究了 miR-1322 的靶基因。此外,我们根据患者的临床记录、细胞计数试剂盒-8、吖啶橙/溴化乙锭双重荧光染色、流式细胞术以及划痕愈合和 Transwell 实验,通过 qRT-PCR 确定了 circ-HOMER1 在 HCC 中的特定功能。值得注意的是,circ-HOMER1 在 HCC 细胞和组织中均上调。这种异常表达模式与肿瘤体积较大、肿瘤-淋巴结-转移分期较高以及 HCC 患者预后较差密切相关。此外,沉默 circ-HOMER1 抑制了 HCC 细胞的增殖、迁移和侵袭,并促进了细胞凋亡,反之亦然。从机制上讲,circ-HOMER1 增强了 HCC 中 miR-1322 对 CXCL6 的抑制作用。此外,我们发现 circ-HOMER1 通过 miR-1322/CXCL6 轴促进了 HCC 细胞的生长和侵袭。本研究可为 HCC 患者提供一种潜在的预后指标和治疗靶点。

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