Abstract
Metastasis-associated in colon cancer 1 (MACC1) is a newly identified gene that has been shown to promote tumor cell invasion and metastasis. The present study investigated the effect of MACC1 downregulation on the biological characteristics of the ovarian cancer OVCAR3 cell line. In this study, MACC1 expression was blocked using the RNA interference technique. The downregulation of MACC1 mRNA and protein expression was confirmed using quantitative polymerase chain reaction and western blot analysis. The proliferative activity and adhesion rate of the cells were detected using cell counting kit-8 and a cell adhesion assay, while cell invasion was determined using a Matrigel invasion assay and migration capacity was observed using migration and wound-healing assays. A tube formation assay was also used to examine the angiogenic capacity of cells, and a luciferase assay was performed to assess whether MACC1 binds to the c-MET gene. The MACC1 mRNA and protein expression levels were significantly downregulated using sequence-specific small interfering RNA (siRNA). The inhibition of MACC1 expression markedly decreased the invasive, metastatic and angiogenic capacities of the cells, but only slightly inhibited growth and adhesion. In addition, a putative MACC1-binding site was identified in the 3′-untranslated region of c-MET. MACC1-siRNA was also found to significantly reduce the expression of the c-MET protein and a luciferase reporter assay confirmed that c-MET was the target gene of MACC1. These results demonstrated that the attenuation of MACC1 suppresses cell invasion and migration and that MACC1 may regulate cell metastasis through targeting the expression of c-MET. Inhibition of the function of MACC1 may represent a new strategy for treating ovarian cancer.
Highlights
Ovarian cancer is the fifth leading cause of cancer‐related mortality in females in the USA
A luciferase reporter assay and western blot analysis were used to confirm whether Metastasis‐associated in colon cancer 1 (MACC1) functions as a metastatic promoter in ovarian cancer by targeting c‐MET
MACC1 protein expression was decreased, with an average inhibition of 55.3% in the MACC1‐small interfering RNA (siRNA) group (Fig. 1B). These results indicated that MACC1‐siRNA effectively suppresses MACC1 expression at the mRNA and protein levels in cells
Summary
Ovarian cancer is the fifth leading cause of cancer‐related mortality in females in the USA. Metastasis‐associated in colon cancer 1 (MACC1) [3] was initially shown to promote the metastatic capacities of colorectal cancer, and clinical studies have indicated that it may be an independent prognostic indicator of recurrence and disease‐free survival (DFS). Various studies have revealed that the hepatocyte growth factor (HGF)/c‐MET signaling pathway is key in carcinogenesis [7,8]. MACC1 is a transcription factor that binds to the promoter of c‐MET to stimulate its transcription, leading to the activation of the HGF/c‐MET signaling pathway. A luciferase reporter assay and western blot analysis were used to confirm whether MACC1 functions as a metastatic promoter in ovarian cancer by targeting c‐MET
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