Wednesday, May 19, 2021

Overexpression of ING3 is associated with attenuation of migration and invasion in breast cancer

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Exp Ther Med. 2021 Jul;22(1):699. doi: 10.3892/etm.2021.10131. Epub 2021 May 2.

ABSTRACT

Inhibitor of growth 3 (ING3) has been identified as a potential cancer drug target, but little is known about its role in breast cancer. Thus, the present study aimed to investigate ING3 expression in breast cancer, its clinical value, and how ING3 influences the migration and invasion of breast cancer cells. The Cancer Genome Atlas and UALCAN databases were used to analyze ING3 expression in cancer tissues and normal tissues. Survival analysis was performed using the UALCAN, UCSC Xena and KM-plot databases. In addition, reverse transcription-quantitative PCR and western blot analyses were performed to detect ING3 mRNA and protein expression levels. ING3 was overexpressed via lentiviral vector transfection, while the Transwell and wound healing assays were performed to assess the cell migratory and invasive abilities. Protein i nteraction and pathway analyses were performed using the GeneMANIA and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The results demonstrated that ING3 expression was significantly lower in cancer tissues compared with normal tissues (P<0.05). In addition, luminal A and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer tissues expressed lower levels of ING3 compared with normal breast tissues. Notably, statistically significant differences were observed in long-term survival between patients with luminal A (P=0.04) and HER2-enriched (P=0.008) breast cancer, with high and low expression levels of ING3. The results of the Transwell migration and invasion assays demonstrated that overexpression of ING3 significantly inhibited the migratory and invasive abilities of MCF7 (P<0.05) and HCC1937 (P<0.05) cells. The results of the wound healing assay demonstrated that the percentage wound closure significantly decreased in cells transfected with LV5-ING3 compared with the negative control group at 12 h (P<0.05) and 24 h (P<0.01). The PI3K/AKT, JAK/STAT, NF-κB and Wnt/β-catenin pathways are the potential pathways regulated by ING3. Notably, overexpression of ING3 inhibited migration and invasion in vitro. However, further studies are required to determine whether ING3 regulates the biological behavior of breast cancer via tumor-related pathways.

PMID:34007308 | PMC:PMC8120550 | DOI:10.3892/etm.2021.10131

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