The cluster of miR-143 and miR-145 affects the risk for esophageal squamous cell carcinoma through co-regulating fascin homolog 1.

The cluster of miR-143 and miR-145 affects the risk for esophageal squamous cell carcinoma through co-regulating fascin homolog 1.
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miR-143 和 miR-145 簇通过共同调节 Fascin 同源物 1 影响食管鳞状细胞癌的风险

DOI:
10.1371/journal.pone.0033987
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Yin L
Yin L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu R;Liao J;Yang M;Sheng J;Yang H;Wang Y;Pan E;Guo W;Pu Y;Kim SJ;Yin L

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MicroRNAs (miRNAs)是一种18-24 nt非编码rna,被认为在细胞增殖、分化、凋亡和发育中起重要作用。最近的研究表明,一些已知的microrna在一个单一的多顺反子转录本中映射到一个单一的基因组区域。但该星团的作用仍不得而知。为了了解miR-143和miR-145在食管鳞状细胞癌(ESCC)中的作用和机制,通过病例对照研究评估ESCC患者成熟miR-143和miR-145表达与食管癌风险的关系,并利用3'UTR荧光素酶报告基因法分析ESCC细胞系中成熟miRNA调控的靶蛋白。采用实时反转录PCR技术检测110对食管癌组织及癌旁正常组织中miR-143和miR-145的表达水平。miR-143和miR-145的相对表达量在癌组织和匹配对照组之间有统计学差异。miR-143和miR-145的联合表达与食管癌的发生风险显著相关。同时,两种mirna在肿瘤患者体内的表达降低,推测有淋巴结转移的趋势。采用Pearson相关分析miR-143和miR-145的共表达模式。结果表明,这两种mirna在组织和肿瘤细胞系中的表达均有显著相关性。3'UTR荧光素酶报告基因检测表明,fastin Homolog 1 (FSCN1)可被miR-143和miR-145共同调控。Western blotting分析显示,FSCN1蛋白水平与ESCC细胞系中miR-143和miR-145的表达无显著的线性相关。综上所述,由于miR-143和miR-145可调控致癌FSCN1并参与转移调节,因此本研究提示miR-143和miR-145组合变量可作为食管癌早期诊断和预后的潜在生物标志物。
MicroRNAs (miRNAs), 18–24 nt non-coding RNAs, are thought to play important roles in cell proliferation, differentiation, apoptosis, and development. Recent studies suggest that some of the known microRNAs map to a single genomic locale within a single polycistronic transcript. But the roles of the cluster remain to be known. In order to understand the role and mechanism of a cluster of miR-143 and miR-145 in esophageal squamous cell carcinoma (ESCC), the association of mature miR-143 and miR-145 expression with the risk for esophageal cancer was evaluated in ESCC patients with a case-control study, and target protein regulated by mature miRNA was analyzed in ESCC cell lines with 3′UTR luciferase reporter assay. The expression levels of miR-143 and miR-145 were determined in 110 pairs of esophageal cancer tissues and adjacent normal tissues using real-time reverse transcription PCR. The relative expression of miR-143 and miR-145 were statistically different between cancer tissues and matched controls. The combined expression of miR-143 and miR-145 was significantly associated with the risk for esophageal cancer. Meanwhile, the reduced expression of two miRNAs in tumor patient was supposed to have a trend of lymph node metastases. The co-expression pattern of miR-143 and miR-145 was analyzed with Pearson correlation. It showed a significant correlation between these two miRNAs expression both in tissues and tumor cell lines. 3′UTR luciferase reporter assay indicated that Fascin Homolog 1 (FSCN1) could be co-regulated by miR-143 and miR-145. The protein level of FSCN1 showed no significant linear correlation with miR-143 and miR-145 expression in ESCC cell lines with Western blotting analysis. In conclusion, since miR-143 and miR-145 could regulate oncogenic FSCN1 and take part in the modulation of metastases, the result suggested the combination variable of miR-143 and miR-145 as a potential biomarker for earlier diagnosis and prognosis of esophageal cancer.
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