miR-320a 调控高迁移率族蛋白 B1 的表达并抑制肝癌的侵袭和转移。
miR-320a regulates high mobility group box 1 expression and inhibits invasion and metastasis in hepatocellular carcinoma.
机构信息
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
Academy of Traditional Chinese Medicines, Harbin, China.
出版信息
Liver Int. 2017 Sep;37(9):1354-1364. doi: 10.1111/liv.13424. Epub 2017 Apr 11.
BACKGROUND & AIMS: Several studies have shown that miR-320a induces apoptosis, inhibits cell proliferation, and affects cell cycle progression as a tumour suppressor in many cancers. However, the involvement of miR-320a in the invasion and metastasis of hepatocellular carcinoma (HCC) is still unknown.
METHODS
Endogenous miR-320a and high mobility group box 1 (HMGB1) expressions were assayed by real-time PCR. Luciferase activities were measured using a dual-luciferase reporter assay system. Western blots were used to determine the protein expressions of HMGB1, MMP2, and MMP9. Invasion and metastasis of tumour cells were, respectively, evaluated by the transwell invasion assay and the wound healing assay.
RESULTS
The expression of miR-320a was significantly decreased in 24 of 32 (75%) HCC tissues and associated with the invasion and metastasis of HCC. Furthermore, we demonstrated that HMGB1 was a direct target of miR-320a and there was a significant negative correlation between miR-320a and HMGB1 expression in HCC. Ectopic expression or inhibition of miR-320a potently regulated the invasion and metastasis of HCC cells in HMGB1-dependent manner.
CONCLUSIONS
Our results showed that miR-320a was involved in the invasion and metastasis by targeting HMGB1 and had an anti-metastasis effect in HCC.
背景与目的
多项研究表明，miR-320a 作为一种肿瘤抑制因子，在多种癌症中诱导细胞凋亡、抑制细胞增殖并影响细胞周期进程。然而，miR-320a 是否参与肝细胞癌（HCC）的侵袭和转移仍不清楚。
方法
通过实时 PCR 检测内源性 miR-320a 和高迁移率族蛋白 B1（HMGB1）的表达。使用双荧光素酶报告基因检测系统测量荧光素酶活性。Western blot 用于检测 HMGB1、MMP2 和 MMP9 的蛋白表达。通过 Transwell 侵袭实验和划痕愈合实验分别评估肿瘤细胞的侵袭和转移。
结果
在 32 个 HCC 组织中的 24 个（75%）中，miR-320a 的表达明显降低，并且与 HCC 的侵袭和转移相关。此外，我们证明 HMGB1 是 miR-320a 的直接靶标，在 HCC 中 miR-320a 和 HMGB1 的表达之间存在显著的负相关。外源性表达或抑制 miR-320a 能够以 HMGB1 依赖的方式有力地调节 HCC 细胞的侵袭和转移。
结论
我们的研究结果表明，miR-320a 通过靶向 HMGB1 参与了 HCC 的侵袭和转移，并且在 HCC 中具有抗转移作用。
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