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miR-126表达失调在结直肠癌发病机制中的作用及其临床意义

Deregulation of miR-126 expression in colorectal cancer pathogenesis and its clinical significance.

作者信息

Ebrahimi Faeza, Gopalan Vinod, Wahab Riajul, Lu Cu-Tai, Smith Robert Anthony, Lam Alfred King-Yin

机构信息

Cancer Molecular Pathology, School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.

Cancer Molecular Pathology, School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia; School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.

出版信息

Exp Cell Res. 2015 Dec 10;339(2):333-41. doi: 10.1016/j.yexcr.2015.10.004. Epub 2015 Oct 9.

Abstract

In this study, we investigated the expression profiles and clinicopathological significance of miR-126 in large cohort of patients with colorectal cancers as well the cellular repercussions of miR-126 in colon cancer cells along with its targets in-vitro. Down regulation of miR-126 expression was associated with histological subtypes, peri-neural tumour infiltration, microsatellite instability and pathological staging of colorectal cancers (p<0.05). Low miR-126 expression was also associated with poorer survival in patients with colorectal cancer. Analysis of matched tissues from the same patient revealed that approximately 70% of the tested patients had similar levels of expression of miR-126 in primary cancer and cancer metastases in both lymph node and distant metastases. In addition, induced overexpression of miR-126 showed reduced cell proliferation, increased apoptosis and decreased accumulation of cells in the G0-G1 phase of the colon cancer cells. Furthermore, SW480(+miR-126) cells showed reduced BCL-2 and increased P53 protein expression. To conclude, deregulation of miR-126 in colorectal cancer at the tissue and cellular levels as well as its correlation with various clinicopathological parameters confirm the cancer suppressive role of miR-126 in colorectal cancer.

摘要

在本研究中,我们调查了大量结直肠癌患者队列中miR-126的表达谱及其临床病理意义,以及miR-126在结肠癌细胞中的细胞效应及其体外靶点。miR-126表达下调与结直肠癌的组织学亚型、神经周围肿瘤浸润、微卫星不稳定性及病理分期相关(p<0.05)。miR-126低表达还与结直肠癌患者较差的生存率相关。对同一患者的配对组织分析显示,约70%的受试患者在原发性癌以及淋巴结和远处转移的癌转移灶中miR-126表达水平相似。此外,miR-126的诱导过表达显示结肠癌细胞的细胞增殖减少、凋亡增加以及G0-G1期细胞积累减少。此外,SW480(+miR-126)细胞显示BCL-2表达降低,P53蛋白表达增加。总之,miR-126在结直肠癌组织和细胞水平的失调及其与各种临床病理参数的相关性证实了miR-126在结直肠癌中的抑癌作用。

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