MIIP inhibits malignant progression of hepatocellular carcinoma through regulating AKT
Authors: P Yang
S-S Peng
J Fang
Y-L Chen
H-B Yao
Z-Y Ding
Journal: European Review for Medical and Pharmacological Sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MIIP; hepatocellular carcinoma; AKT; expression characteristics; malignant progression
Affiliations: Department of General Surgery, 988 Hospital of the People's Liberation Army, Zhengzhou, China. .

Abstract:  Objective: 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. Patients and methods: 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. Results: 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. Conclusions: 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. 

Retracted: No

PubPeer comments:
  The collection of clinical specimens was approved by the Ethics Monitoring Committee ... The six authors claim a total of seven affiliations: 988 Hospital of the People s Liberation Army, Zhengzhou; Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou; Second Affiliated Hospital of Guilin Medical College, Guilin; Huangshi Central Hospital of Edong Healthcare Group, Hubei Polytechnic University, Huangshi; Wuhan University of Science and Technology, Wuhan; Mianyang Central Hospital, Sichuan Province, Mianyang; WuXi Traditional Chinese Medicine Hospital Affiliated by Nanjing TCM University, Wuxi. We are left completely in the dark as to where patients were actually recruited, and *which* Ethics committee gave approval. Figs 1D, 3F.  Kaplan Meier survival curve of patients with hepatocellular carcinoma based on MIIP expression was shown; the prognosis of patients with low expression was found significantly worse than that of high expression group ....  Kaplan Meier survival curve of patients with hepatocellular carcinoma based on AKT expression was shown; the prognosis of patients with high expression was found significantly worse than that of low expression group .  Clearly the overall survival for the 39 patients is lower when they are dichotomised into high- and low-MIIP expression groups than when dichotomised into high- and low-AKT levels, so the latter is definitely preferable. Please compare with Figs 1D and 3C from [Cui et al (2020)] .  Kaplan Meier survival curve of bladder cancer patients based on HOXA10 expression; the prognosis of patients with high expression was significantly worse than that of low expression group ...  Kaplan Meier survival curve of bladder cancer patients based on FOSL1 expression was shown; the prognosis of patients with low expression was significantly worse than that of high expression group .  3C and 3F appear to be identical. Both Figs 1D are manifestations of  Hoya s Law for J.BUOn ERMPS :  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given noncoding RNA, survival rate for one half-group or both *always* drops to 0% at 75 months. Some other examples, from left to right: - Fig 1 from [Zang et al (2020)] - Fig 1 from [Li et al (2020)] - Fig 1, and Fig 4D, from [Cui et al (2019)] - Fig 1D from [Gao et al (2019)] .  *[left]* Figure 1C from [Wu et al (2020)] . *[right]* Figs 1D, 3E from [Wu et al (2019)] .  1D from [Luo, Yan Liu] :  , 
 *[right]* Fig 3D from [Fang et al (2020)] .  There was a significant negative correlation between the expression levels of MIIP and AKT in hepatocellular carcinoma tissues . *[left]* Fig 3D from [Tan, Ni Xiong (2020)] .  Significant negative correlation between UNC5B-AS1 and caspase-9 expression levels in prostate cancer tissues .  Implausible number of points in common. ,