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RNA:乳腺癌预后的新生物标记物

来源:生物谷 2013-11-13 20:47

2013年11月14日讯 /生物谷BIOON/--近日,昆士兰州科学家已经确定了一个基因“开关”,可以预示乳腺癌是否会蔓延。QIMR Berghofer医学研究所发现,一个特定的RNA(核糖核酸)分子(miR-139-5p)在侵略性癌症中是缺少的。

博士Nicole Cloonan说,这一发现可能更好地对乳腺癌患者进行预后分析,并最终发展新的治疗方法。从本质上讲,这个特定的基因片段或miR-139-5p在我们的遗传程序(genetic program)通常就像“紧急制动”,确保我们的细胞继续正常繁殖。

但现在发现这个“紧急刹车”miR-139-5p在侵略性乳腺癌中是不存在的,因此,在癌症测试中,这一“紧急刹车”将是一个明确的标记物,预示肿瘤是否可能蔓延。

乳腺癌是妇女最常见的癌症。患者生存期的长段取决于癌症被何时诊断,一旦发生转移,患者5年生存率仅为21%。博士Cloonan说:我们知道,原发性乳腺癌很少杀导致患者死亡,那些侵略性的肿瘤蔓延或肿瘤发生转移是导致患者预后不良的主要原因。

这个研究具有广泛的影响,虽然科学家现在专注于乳腺癌中的“紧急刹车”microRNA,但“紧急刹车”miR-139-5p或许也在恶性肝癌,胃癌,脑癌和皮肤癌中缺少。新发现的miR-139-5p曾经被认识是我们遗传程序中的“垃圾”。但近年来,科学家已经认识到他在癌症中发挥的推动作用。(生物谷Bioon.com)

miR-139-5p is a regulator of metastatic pathways in breast cancer

Keerthana Krishnan, Anita L. Steptoe, Hilary C. Martin, et al

Metastasis is a complex, multistep process involved in the progression of cancer from a localized primary tissue to distant sites, often
characteristic of the more aggressive forms of this disease. Despite being studied in great detail in recent years, the mechanisms that
govern this process remain poorly understood. In this study, we identify a novel role for miR-139-5p in the inhibition of breast
cancer progression. We highlight its clinical relevance by reviewing miR-139-5p expression across a wide variety of breast
cancer subtypes using in-house generated and online data sets to show that it is most frequently lost in invasive tumors. A biotin
pull-down approach was then used to identify the mRNA targets of miR-139-5p in the breast cancer cell line MCF7. Functional
enrichment analysis of the pulled-down targets showed significant enrichment of genes in pathways previously implicated in
breast cancer metastasis (P < 0.05). Further bioinformatic analysis revealed a predicted disruption to the TGFβ, Wnt, Rho, and
MAPK/PI3K signaling cascades, implying a potential role for miR-139-5p in regulating the ability of cells to invade and migrate.
To corroborate this finding, using the MDA-MB-231 breast cancer cell line, we show that overexpression of miR-139-5p results
in suppression of these cellular phenotypes. Furthermore, we validate the interaction between miR-139-5p and predicted
targets involved in these pathways. Collectively, these results suggest a significant functional role for miR-139-5p in breast
cancer cell motility and invasion and its potential to be used as a prognostic marker for the aggressive forms of breast cancer.

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