Abstract
BackgroundMyofibrillogenesis regulator 1 (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, the significance of MR-1 in human ovarian cancer has not yet been explored. The aim of this study was to examine whether MR-1 is a predictor of ovarian cancer and its value as a therapeutic target in ovarian cancer patients.MethodsReverse-transcription polymerase chain reaction (PCR) and quantitative real-time PCR were used to detect MR-1 mRNA levels in tissue samples from 26 ovarian cancer patients and 25 controls with benign ovarian disease. Anti-MR-1 polyclonal antibodies were prepared, tested by ELISA and western blotting, and then used for immunohistochemical analysis of the tissue samples. Adhesion and invasion of 292T cells was also examined after transfection of a pMX-MR-1 plasmid. Knockdown of MR-1 expression was achieved after stable transfection of SKOV3 cells with a short hairpin DNA pGPU6/GFP/Neo plasmid against the MR-1 gene. In addition, SKOV3 cells were treated with paclitaxel and carboplatin, and a potential role for MR-1 as a therapeutic target was evaluated.ResultsMR-1 was overexpressed in ovarian cancer tissues and SKOV3 cells. 293T cells overexpressed MR-1, and cellular spread and invasion were enhanced after transfection of the pMX-MR-1 plasmid, suggesting that MR-1 is critical for ovarian cancer cell growth. Knockdown of MR-1 expression inhibited cell adhesion and invasion, and treatment with anti-cancer drugs decreased its expression in cancer cells. Taken together, these results provide the first evidence of the cellular and molecular mechanisms by which MR-1 might serve as a novel biological marker and potential therapeutic target for ovarian cancer.ConclusionsMR-1 may be a biomarker for diagnosis of ovarian cancer. It may also be useful for monitoring of the effects of anti-cancer therapies. Further studies are needed to clarify whether MR-1 is an early diagnostic marker for ovarian cancer and a possible therapeutic target.
Highlights
Myofibrillogenesis regulator 1 (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth
MR-1 Is Differentially Expressed in Human Malignant and Benign Ovarian Tumors Tissue MR-1 mRNA levels were analyzed by RT-polymerase chain reaction (PCR) and quantitative real-time PCR to investigate the expression of MR-1 in malignant and benign ovarian tumors
RT-PCR showed that the mRNA expression level was higher in ovarian cancer patients than in controls (Figure 1A)
Summary
Myofibrillogenesis regulator 1 (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. Myosin light chain-2 (MLC2) plays an important role in cell migration from solid tumors such as ovarian cancer, and its dephosphorylation can induce apoptosis [3,4]. A recent report indicated that MLC2 may regulate cell proliferation and migration by interacting with myofibrillogenesis regulator 1 (MR-1) [5]. Overexpression of MR-1 is associated with cancer cell proliferation and migration in human hepatoma HepG2 cells [6]. MR-1 may promote cancer cell proliferation by binding to specific proteins, such as eukaryon initiation factor 3, which is highly associated with the regulation of tumor cell growth and invasion [11]. Overexpression of MR-1 can activate the nuclear factor B signaling pathway, which is linked to a wide variety of diseases including cancer, inflammation and autoimmune disease [12]
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