Department of General Surgery, 988 Hospital of the People's Liberation Army, Zhengzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2335-2346. doi: 10.26355/eurrev_202003_20500.
This study was aimed to investigate the expression characteristics of MIIP in hepatocellular carcinoma (HCC), and to further explore whether it can inhibit the malignant progression of this disease via regulating AKT expression.
Real-time quantitative PCR (qRT-PCR) was performed to examine the expression of MIIP in tumor and paracancerous tissue specimens of 39 patients with HCC, and to analyze the interplay between MIIP expression and clinical indicators and prognosis of HCC patients. At the same time, in HCC cell lines, the expression of MIIP was further verified using qRT-PCR. In addition, MIIP overexpression and knockdown models were constructed using lentivirus in HCC cell lines (Bel-7402 and Hep3B), and the influence of MIIP on the biological function of HCC cells was analyzed through CCK-8 and transwell migration assays. Finally, luciferase reporting assay and cell reverse experiments were applied to further explore the potential molecular mechanism and the interaction between MIIP and AKT.
The results of qRT-PCR showed that the expression level of MIIP in HCC tissue samples was remarkably lower than that in adjacent ones, with a statistically significant difference. Compared with patients with high expression of MIIP, patients with low MIIP expression had a higher occurrence of distant metastasis and a lower overall survival rate. Similarly, compared with control group, the proliferation and migration ability of HCC cells in MIIP knockdown group (sh-MIIP) was remarkably enhanced, while the opposite result was observed in MIIP overexpression group. In addition, qRT-PCR results also revealed that AKT and MIIP were negatively correlated in HCC tissues. At the same time, the results of luciferase reporter gene assay demonstrated that MIIP can be targeted by AKT through certain binding site. Additionally, cell reverse experiment found that there might exist a mutual regulation between MIIP and AKT, thereby jointly regulating the malignant progression of HCC.
MIIP expression is remarkably decreased both in HCC tissues and cell lines; meanwhile, the low expression of MIIP is positively correlated with the occurrence of distant metastasis and poor prognosis of patients with HCC. In addition, MIIP may be able to inhibit the malignant progression of HCC by modulating AKT expression.
本研究旨在探讨 MIIP 在肝细胞癌（HCC）中的表达特征，并进一步探讨其是否能通过调节 AKT 表达来抑制该疾病的恶性进展。
采用实时定量 PCR（qRT-PCR）检测 39 例 HCC 患者肿瘤和癌旁组织标本中 MIIP 的表达，并分析 MIIP 表达与 HCC 患者临床指标和预后的关系。同时，采用 qRT-PCR 进一步验证 HCC 细胞系中 MIIP 的表达。此外，利用慢病毒在 HCC 细胞系（Bel-7402 和 Hep3B）中构建 MIIP 过表达和敲低模型，通过 CCK-8 和 Transwell 迁移实验分析 MIIP 对 HCC 细胞生物学功能的影响。最后，通过 luciferase 报告基因检测和细胞反向实验进一步探讨 MIIP 与 AKT 之间的潜在分子机制及其相互作用。
qRT-PCR 结果显示，与癌旁组织相比，HCC 组织样本中 MIIP 的表达水平明显降低，差异具有统计学意义。与 MIIP 高表达患者相比，MIIP 低表达患者远处转移的发生率更高，总生存率更低。同样，与对照组相比，MIIP 敲低组（sh-MIIP）的 HCC 细胞增殖和迁移能力明显增强，而 MIIP 过表达组则相反。此外，qRT-PCR 结果还显示，AKT 和 MIIP 在 HCC 组织中呈负相关。同时，荧光素酶报告基因检测结果表明，MIIP 可通过特定结合位点被 AKT 靶向。此外，细胞反向实验发现 MIIP 和 AKT 之间可能存在相互调节，从而共同调节 HCC 的恶性进展。
MIIP 在 HCC 组织和细胞系中的表达均显著降低；同时，MIIP 的低表达与 HCC 患者远处转移的发生和不良预后呈正相关。此外，MIIP 可能通过调节 AKT 表达抑制 HCC 的恶性进展。
