Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4.

Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4.
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DOI:
10.1002/cam4.309
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发表时间:
2014-12
期刊:
影响因子:
4
通讯作者:
Iseki, Ken
Iseki, Ken
中科院分区:
医学3区
文献类型:
--
作者:
Jinushi, Takafumi;Shibayama, Yoshihiko;Kinoshita, Ichiro;Oizumi, Satoshi;Jinushi, Masahisa;Aota, Tadahiro;Takahashi, Toshiyuki;Horita, Shoichi;Dosaka-Akita, Hirotoshi;Iseki, Ken

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多梳阻遏物复合物2的一个组成部分,zeste同源物增强子2(EZH 2)在肿瘤恶性和转移中起重要作用,而乳脂球表皮生长因子8(MFGE 8)在肿瘤进展和预后中起关键作用。microRNAs(miRs)也参与了多种生理和病理过程。我们在此评估了结直肠癌患者的总生存期(OS)与可能靶向EZH 2和MFGE 8的癌miR和miR表达之间的关系。血浆和福尔马林固定石蜡包埋(FFPE)样本来自71例结直肠癌患者。评估与EZH 2和MFGE 8 mRNA互补的miR的表达水平和癌症恶性肿瘤。分析的miR如下:miR-16、miR-21、miR-26 a、miR-34 a、miR-98、miR-101- 3 p、miR-101- 5 p、miR-124- 5 p(也称为miR-124*)、miR-126- 3 p、miR-126- 5 p、miR-210、miR-217和miR-630。完全切除患者的MFGE 8血浆表达水平显著低于不可切除患者。miR-124- 5 p在血浆和FFPE样本中的表达水平越高,OS的可能性越高。将模拟miR-124 - 5 p转染到WiDr和COLO 201细胞中,抑制了4号染色体结构维持(SMC 4)mRNA的表达。我们的研究结果表明,miR-124- 5 p可能靶向肿瘤发生基因SMC 4,这表明miR-124- 5 p在血浆和FFPE样本中的表达水平;因此,血浆中MFGE 8、miR-26 a和miR-124- 5 p的表达可用作生物标志物来确定结直肠癌患者的预后。
A component of polycomb repressor complex 2, enhancer of zeste homolog 2 (EZH2), plays an important role in tumor malignancy and metastasis, while milk fat globule-epidermal growth factor-factor 8 (MFGE8) plays a key role in tumor progression and prognosis. MicroRNAs (miRs) are also critically involved in various physiological and pathological processes. We here evaluated the relationship between overall survival (OS) in colorectal cancer patients and the expression of onco-miRs and miRs, which may target EZH2 and MFGE8. Plasma and formalin-fixed paraffin-embedded (FFPE) samples were obtained from 71 colorectal cancer patients. The expression levels of miRs complementary to EZH2 and MFGE8 mRNA and cancer malignancies were evaluated. The miRs analyzed were as follows: miR-16, miR-21, miR-26a, miR-34a, miR-98, miR-101-3p, miR-101-5p, miR-124-5p (also known as miR-124*), miR-126-3p, miR-126-5p, miR-210, miR-217, and miR-630. The plasma expression levels of MFGE8 in completely resected patients were significantly lower than those in unresectable patients. Lower miR-26a expression levels were correlated with a higher probability of OS. Higher miR-124-5p expression levels in plasma and FFPE samples were correlated with a higher probability of OS. The transfection of mimic miR-124-5p into WiDr and COLO201 cells inhibited the expression of structural maintenance of chromosomes 4 (SMC4) mRNA. Our results indicate that miR-124-5p may target the tumorigenesis gene, SMC4, which suggests that expression levels of miR-124-5p in plasma and FFPE samples; therefore, the expression of MFGE8, miR-26a, and miR-124-5p in plasma may be used as biomarkers to determine the prognosis of colorectal cancer patients.
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