Introduction

Globally, hepatocellular carcinoma (HCC) is the sixth most common malignancy and it has the fourth highest mortality. MicroRNAs play a significant part in biological processes in cell formation and advancement by targeting genes in many cancers including HCC.

Objective

In the present study we examine the involvement of miR-4521 and FAM129A correlations in HCC occurrence and progression.

Methods

Expression levels of miR-4521 and FAM129A in HCC tissues and cells were detected. Immunohistochemistry was carried out to detect expression of FAM129A, MMP9 and TIMP-1 in HCC tissues. Western blot assays were used to examine expression levels of different genes involve in signaling pathways. Transwell chamber, MTT and wound healing assays were performed to check cell migration, invasion and proliferation rates.

Results

Overexpression of FAM129A positively correlated with upregulation of MMP9 and negatively correlated with TIMP-1 in HCC patient samples, which encouraged progression and metastasis of HCC. An antagonistic relation between miR-4521 and FAM129A was detected in current study, down-regulation of miR-4521 and up-regulation of FAM129A was demonstrated in HCC tissues and cell lines as compare to normal tissue samples and the normal cell line LO2. Overexpressing miR-4521 and silencing FAM129A impaired HCC cell migratory and invasive properties and suppressed cell proliferation. Mutually, miR-4521-FAM129A axial regulation inhibited in vitro proliferation of cells by promoting apoptosis through the p-FAK/p-AKT/MDM2/P53 and p-FAK/p-AKT/BCL-2/BAX/Cytochrome-C/Caspase-3/Caspase-9 pathways, respectively, and suppressed the migration and invasion capabilities of HCCLM3 and HepG2 cells via the TIMP-1/MMP9/MMP2 and p-FAK/p-AKT pathway.

Conclusion

Our work found the axial regulation mechanism of miR-4521-FAM129A in HCC. Deficiency of miR-4521 and abundance of FAM129A synergistically enhanced cancer progression by increasing cell proliferation and malignant invasion and by inhibiting apoptosis. These discoveries suggest that miR-4521/FAM129A might play a vital role in hepatic cancer progression and could be a candidate for its therapy.

中文翻译：

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MiR-4521 通过靶向 FAM129A 抑制 FAK/AKT 通路的磷酸化，在肝癌细胞的生长和转移中发挥肿瘤抑制作用

介绍

在全球范围内，肝细胞癌 (HCC) 是第六大最常见的恶性肿瘤，死亡率位居第四。MicroRNA通过靶向包括HCC在内的许多癌症中的基因，在细胞形成和发展的生物过程中发挥着重要作用。

客观的

在本研究中，我们检查了 miR-4521 和 FAM129A 相关性在 HCC 发生和进展中的参与。

方法

检测HCC组织和细胞中miR-4521和FAM129A的表达水平。进行免疫组织化学以检测HCC组织中FAM129A、MMP9和TIMP-1的表达。蛋白质印迹分析用于检查涉及信号通路的不同基因的表达水平。进行 Transwell 室、MTT 和伤口愈合测定以检查细胞迁移、侵袭和增殖率。

结果

在 HCC 患者样本中，FAM129A 的过表达与 MMP9 的上调呈正相关，与 TIMP-1 呈负相关，这促进了 HCC 的进展和转移。在当前研究中检测到 miR-4521 和 FAM129A 之间的拮抗关系，与正常组织样品和正常细胞系 LO2 相比，在 HCC 组织和细胞系中证实了 miR-4521 的下调和 FAM129A 的上调。过表达 miR-4521 和沉默 FAM129A 会损害 HCC 细胞的迁移和侵袭特性并抑制细胞增殖。miR-4521-FAM129A 轴向调控通过 p-FAK/p-AKT/MDM2/P53 和 p-FAK/p-AKT/BCL-2/BAX/Cytochrome-C/ 促进细胞凋亡相互抑制体外增殖Caspase-3/Caspase-9 通路，分别

结论

我们的工作发现了 miR-4521-FAM129A 在 HCC 中的轴向调控机制。miR-4521 的缺乏和 FAM129A 的丰富通过增加细胞增殖和恶性侵袭以及通过抑制细胞凋亡来协同促进癌症进展。这些发现表明 miR-4521/FAM129A 可能在肝癌进展中发挥重要作用，并可能成为其治疗的候选者。