miRNA‑222 promotes liver cancer cell proliferation, migration and invasion and inhibits apoptosis by targeting BBC3

Liu,Zhichun; Sun,Jingwu; Liu,Bin; Zhao,Mengjie; Xing,Entao; Dang,Cunshu

doi:10.3892/ijmm.2018.3637

miRNA‑222 promotes liver cancer cell proliferation, migration and invasion and inhibits apoptosis by targeting BBC3

Authors:
- Zhichun Liu
- Jingwu Sun
- Bin Liu
- Mengjie Zhao
- Entao Xing
- Cunshu Dang
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Affiliations: Department of Hepatobiliary Surgery, Central Hospital of China National Petroleum Corporation, Langfang, Hebei 065000, P.R. China
Published online on: April 20, 2018 https://doi.org/10.3892/ijmm.2018.3637
Pages: 141-148
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate molecular mechanisms associated with liver cancer and provide a possible therapeutic target for the treatment of liver cancer. Liver cancer patients that were diagnosed and treated at the Central Hospital of China National Petroleum Corp. were included in the present study. microRNA (miR)‑222 was predicted to target B‑cell lymphoma-2 (Bcl‑2) binding component 3 (BBC3, also known as p53 upregulated modulator of apoptosis) by a bioinformatics analysis with TargetScan, which was verified by a dual‑luciferase reporter assay system. The correlations between BBC3 and miR‑222 levels and the patients' characteristics were analyzed. Furthermore, reverse transcription‑quantitative polymerase chain reaction was used to assess the mRNA levels of miRNA‑222 in the HCC‑LM3, MHCC97H and HepG2 cell lines. HepG2 cells were then transfected with miR‑222 inhibitor or miR‑negative control inhibitor. Cell proliferation, apoptosis, cell cycle, migration and invasion were evaluated by an MTT assay, flow cytometry, wound healing assay and Transwell assay, respectively. BBC3 was quantified by immunofluorescence and western blot analysis, and cyclin D1, Bcl‑2 and caspase‑3 levels were also evaluated by western blotting. miR‑222 inhibitor obviously inhibited HepG2 cell proliferation, migration, invasion, BBC3 and cyclin D1 protein expression levels and enhanced HepG2 cell apoptosis as well as the protein levels of Bcl‑2 and caspase‑3. miR‑222 level in tumors ≥5 cm (maximum) was significantly higher compared with tumors <5 cm (maximum) and was significantly higher in metastatic tumors compared with non‑metastatic tumors, while BBC3 level showed the adverse changes. The results of the present study suggested that miR‑222 inhibitor exerted anti‑cancer effects against liver cancer cells, probably by targeting the 3' untranslated region (UTR) of BBC3.

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