Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer.

Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer.
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DOI:
10.1186/1471-2407-11-270
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发表时间:
2011-06-25
期刊:
影响因子:
3.8
通讯作者:
Guo L
Guo L
中科院分区:
医学2区
文献类型:
--
作者:
Lu R;Sun M;Feng J;Gao X;Guo L

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肌原纤维生成调节因子1 (Myofibrillogenesis regulator 1, MR-1)在人类癌细胞中过表达,在癌细胞生长中起重要作用。然而,MR-1在人类卵巢癌中的意义尚未被探索。本研究的目的是研究MR-1是否是卵巢癌的预测因子及其作为卵巢癌患者治疗靶点的价值。采用反转录聚合酶链反应(PCR)和实时荧光定量PCR技术检测26例卵巢癌患者和25例良性卵巢疾病对照组织标本中MR-1 mRNA水平。制备抗mr -1多克隆抗体,经ELISA和western blotting检测,对组织样品进行免疫组化分析。转染pMX-MR-1质粒后,还检测了292T细胞的粘附和侵袭。用短发夹DNA pGPU6/GFP/Neo质粒稳定转染SKOV3细胞,抑制MR-1基因的表达。此外,用紫杉醇和卡铂治疗SKOV3细胞,并评估MR-1作为治疗靶点的潜在作用。MR-1在卵巢癌组织和SKOV3细胞中过表达。转染pMX-MR-1质粒后,293T细胞过表达MR-1,细胞扩散和侵袭增强,提示MR-1对卵巢癌细胞生长至关重要。下调MR-1表达可抑制细胞粘附和侵袭,抗癌药物治疗可降低其在癌细胞中的表达。综上所述,这些结果为MR-1可能作为卵巢癌新的生物标志物和潜在治疗靶点的细胞和分子机制提供了第一个证据。MR-1可能是卵巢癌诊断的生物标志物。它也可用于监测抗癌治疗的效果。需要进一步的研究来阐明MR-1是否是卵巢癌的早期诊断标志物和可能的治疗靶点。
Myofibrillogenesis 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. Reverse-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. MR-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. MR-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.
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