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Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer

机译:microRNA-29家族表达的特征及其在胃癌中的作用机制研究

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摘要

Increasing evidence shows that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. They might be the novel biomarkers or therapeutic targets in disease treatment. miR-29 family was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in gastric cancer (GC) are not well known. Here, we found that the expression of miR-29 family members was significantly reduced in GC compared with adjacent controls. Among them, miR-29c had the most reduced percentage in GC and was associated with aggressive and progressive phenotypes of GC. We further demonstrated that miR-29 family acted as tumor suppressors through targeting CCND2 and matrix metalloproteinase-2 genes in GC. Moreover, the inverse relationship between miR-29 family and their targets was verified in patients and xenograft mice. Finally, reintroduction of miR-29 family significantly inhibited tumor formation of GC cells in the xenograft mice. Take together, our finding characterized the expression properties of miR-29 family, contributed to the function and molecular mechanism of miR-29 family in GC and implied that miR-29 family might be employed as novel prognostic markers and therapeutic targets of GC.
机译:越来越多的证据表明,异常的microRNA(miRNA)表达与肿瘤发生有关。它们可能是疾病治疗中的新型生物标志物或治疗靶标。以前有报道说miR-29家族在多种癌症中起着抑癌或癌基因的作用。然而,它们在胃癌(GC)中的准确表达,功能和机制尚不为人所知。在这里,我们发现与相邻的对照相比,miR-29家族成员的表达在GC中显着降低。其中,miR-29c在GC中的百分比降低最多,并且与GC的侵袭性和进行性表型有关。我们进一步证明,miR-29家族通过靶向GC中的CCND2和基质金属蛋白酶2基因而充当肿瘤抑制因子。而且,在患者和异种移植小鼠中证实了miR-29家族与其靶标之间的逆向关系。最后,miR-29家族的重新引入显着抑制了异种移植小鼠中GC细胞的肿瘤形成。综上所述,我们的发现表征了miR-29家族的表达特性,有助于miR-29家族在GC中的功能和分子机制,并暗示miR-29家族可以用作GC的新的预后标志物和治疗靶标。

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