MicroRNA-328-3p inhibits malignant progression of hepatocellular carcinoma by regulating MMP-9 level
Authors: J-Z Li
J Li
B-Z Liu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-328-3p; hepatocellular carcinoma; proliferation; apoptosis; regulatory mechanisms
Affiliations: Department of Ultrasonography, Jinan Infectious Disease Hospital Affiliated to Shandong University, Jinan, China. .

Abstract:  Objective: This study aims to explore the influence of microRNA-328-3p on proliferative and apoptotic abilities of hepatocellular carcinoma (HCC) cells, and the potential regulatory mechanisms. Patients and methods: Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of microRNA-328-3p in 52 tumor tissue samples and paracancerous ones of HCC patients. The potential interaction between microRNA-328-3p level and clinical indicators of HCC patients was analyzed. Subsequently, the microRNA-328-3p overexpression model was established. In addition, the influence of microRNA-328-3p on the biological functions of the HCC cells was analyzed by the cell counting kit-8 (CCK-8), colony formation assay, and flow cytometry. Finally, the potential downstream gene of microRNA-328-3p was explored by bioinformatics analysis. Recovery experiments were performed to explore the regulation mechanism. Results: QRT-PCR results revealed that microRNA-328-3p level in tumor tissue specimens of HCC patients was remarkably lower than that in adjacent ones, and the difference was statistically significant. Compared with patients with high expression of microRNA-328-3p, those with low expression of miR-328-3p had more advanced pathological staging and lower overall survival. The overexpression of microRNA-328-3p decreased the proliferative capacity and increased apoptotic rate in HCC cells. Subsequently, MMP-9 expression was found to be highly expressed in HCC tissues and cells, and negatively correlated with microRNA-328-3p level. In addition, microRNA-328-3p overexpression significantly down-regulated the protein expressions of CD31, Ki-67, c-Myc, MMP-2, and MMP-9. In the cell reverse experiment, the overexpression of MMP-9 could counteract the influence of the overexpressed microRNA-328-3p on proliferation and apoptosis in HCC cells, so as to regulate the malignant progression of HCC. Conclusions: MicroRNA-328-3p could inhibit the malignant progression of HCC. Its level is remarkably associated with the pathological staging and prognosis of HCC patients. In addition, it is found that microRNA-328-3p might suppress the proliferative ability and promote apoptosis of HCC cells via modulating MMP-9. 

Retracted: No

PubPeer comments:
 Fig 3F.  The Kaplan-Meier survival curves of the hepatocellular carcinoma patients based on the MMP-9 expression . ![file] Another manifestation of Hoya s Law for J.BUOn and ERMPS...  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given nc-RNA, survival rate for one half-group or both will drop to 0% at 75 months. 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)] . ![file] *[left]* Figure 1C from [Wu et al (2020)] . *[right]* Figs 1D, 3E from [Wu et al (2019)] . ![file] , 
 *[right]* Fig 3E from [Li, Li Liu (2019)] .  A significant negative correlation between miR-328-3p and MMP-9 expression levels in the hepatocellular carcinoma tissues . *[left]* Fig 3E from [Fang et al (2020)] .  A negative correlation between expression levels of circ_0005075 and SIRT1 in glioma tissues. ![file] No comment required. ,