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肌原纤维发生调节因子 1(MR-1)是一种新型的人卵巢癌生物标志物和潜在治疗靶点。

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

机构信息

Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.

出版信息

BMC Cancer. 2011 Jun 25;11:270. doi: 10.1186/1471-2407-11-270.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

肌球蛋白纤维生成调节因子 1(MR-1)在人类癌细胞中过度表达,在癌细胞生长中发挥重要作用。然而,MR-1 在人卵巢癌中的意义尚未被探索。本研究旨在研究 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。

方法

采用逆转录聚合酶链反应(PCR)和实时定量 PCR 检测 26 例卵巢癌患者和 25 例良性卵巢疾病对照组织样本中的 MR-1 mRNA 水平。制备抗 MR-1 多克隆抗体,通过 ELISA 和 Western blot 进行检测,然后用于组织样本的免疫组织化学分析。转染 pMX-MR-1 质粒后,还检测了 292T 细胞的黏附和侵袭。通过转染针对 MR-1 基因的短发夹 DNA pGPU6/GFP/Neo 质粒,稳定转染 SKOV3 细胞以敲低 MR-1 表达。此外,用紫杉醇和卡铂处理 SKOV3 细胞,评估 MR-1 作为治疗靶点的潜在作用。

结果

MR-1 在卵巢癌组织和 SKOV3 细胞中过度表达。293T 细胞过表达 MR-1,转染 pMX-MR-1 质粒后细胞扩散和侵袭增强,表明 MR-1 对卵巢癌细胞生长至关重要。敲低 MR-1 表达抑制细胞黏附和侵袭,用抗癌药物处理可降低癌细胞中其表达。综上所述,这些结果提供了 MR-1 作为新型生物标志物和卵巢癌潜在治疗靶点的细胞和分子机制的初步证据。

结论

MR-1 可能是卵巢癌诊断的生物标志物。它也可能有助于监测抗癌治疗的效果。需要进一步研究以阐明 MR-1 是否是卵巢癌的早期诊断标志物和可能的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c9/3132198/775b6d1e54f6/1471-2407-11-270-1.jpg

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