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miRNA-15a-3p 通过与 HMOX1 相互作用抑制肝癌的转移。

MiRNA-15a-3p inhibits the metastasis of hepatocellular carcinoma by interacting with HMOX1.

机构信息

Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12694-12700. doi: 10.26355/eurrev_202012_24167.

DOI:10.26355/eurrev_202012_24167
PMID:33378016
Abstract

OBJECTIVE

To uncover the relationship between microRNA-15a-3p (miRNA-15a-3p) level and clinical features of hepatocellular carcinoma (HCC), and to explore the influence of miRNA-15a-3p on metastasis of HCC cells.

PATIENTS AND METHODS

HCC and paracancerous tissues were surgically resected from 44 HCC patients. Their clinical data and follow-up files were recorded. Differential expressions of miRNA-15a-3p in HCC samples were determined. The relationship between miRNA-15a-3p level and clinical features of HCC patients was analyzed. Changes in proliferative, migratory and invasive potentials in Huh7 and HepG2 cells overexpressing miRNA-15a-3p were examined. The downstream gene of miRNA-15a-3p and its involvement in HCC development were finally explored.

RESULTS

MiRNA-15a-3p was downregulated in HCC tissues. High metastasis rate and poor prognosis were observed in HCC patients expressing a low level of miRNA-15a-3p. Overexpression of miRNA-15a-3p attenuated proliferative, migratory and invasive potentials in HCC. Protein levels of HMOX1, CD31, c-Myc, MMP-2 and MMP-9 were downregulated in HCC cells after overexpression of miRNA-15a-3p. HMOX1 was the downstream gene of miRNA-15a-3p, which was upregulated in HCC samples. Highly expressed HMOX1 was unfavorable to the prognosis in HCC. Overexpression of HMOX1 abolished the regulatory effects of miRNA-15a-3p on HCC cell phenotypes.

CONCLUSIONS

MiRNA-15a-3p is closely linked to lymphatic metastasis, distant metastasis and poor prognosis in HCC. It inhibits the malignant development of HCC by interacting with HMOX1.

摘要

目的

揭示 microRNA-15a-3p(miRNA-15a-3p)水平与肝细胞癌(HCC)临床特征之间的关系,并探讨 miRNA-15a-3p 对 HCC 细胞转移的影响。

患者与方法

对 44 例 HCC 患者的 HCC 及癌旁组织进行手术切除,记录其临床资料及随访资料。检测 HCC 样本中 miRNA-15a-3p 的差异表达情况,分析 miRNA-15a-3p 水平与 HCC 患者临床特征的关系。观察过表达 miRNA-15a-3p 后 Huh7 和 HepG2 细胞增殖、迁移和侵袭能力的变化,最后探讨 miRNA-15a-3p 的下游基因及其在 HCC 发生发展中的作用。

结果

miRNA-15a-3p 在 HCC 组织中呈下调表达。miRNA-15a-3p 低表达的 HCC 患者转移率高,预后差。过表达 miRNA-15a-3p 可减弱 HCC 细胞的增殖、迁移和侵袭能力。过表达 miRNA-15a-3p 后 HCC 细胞中 HMOX1、CD31、c-Myc、MMP-2 和 MMP-9 的蛋白水平下调。HMOX1 是 miRNA-15a-3p 的下游基因,在 HCC 样本中上调,高表达 HMOX1 不利于 HCC 的预后。过表达 HMOX1 可消除 miRNA-15a-3p 对 HCC 细胞表型的调节作用。

结论

miRNA-15a-3p 与 HCC 淋巴结转移、远处转移和不良预后密切相关,通过与 HMOX1 相互作用抑制 HCC 的恶性发展。

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