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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Significance of miR-148a in colorectal neoplasia: Downregulation of miR-148a contributes to the carcinogenesis and cell invasion of colorectal cancer
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Significance of miR-148a in colorectal neoplasia: Downregulation of miR-148a contributes to the carcinogenesis and cell invasion of colorectal cancer

机译：miR-148a在大肠肿瘤中的意义：miR-148a的下调有助于大肠癌的发生和侵袭

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Objective: Colorectal cancer (CRC) develops through the deregulation of gene expression and the accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development, where they can act as oncogenes or oncosuppressors. Methods: miR-148a expression was measured by qRT-PCR in patients with colorectal adenoma (n = 21) and CRC (stage I-IV, n = 159) using formalin-fixed paraffin-embedded tissue samples. In situ hybridization (ISH) using an miR-148a-specific probe was also performed. To further confirm the direct effect of miR-148a on matrix metalloproteinase (MMP)7 expression in CRC, MTT and cell invasion assays using HT29 and WiDr cells were performed. Results: miR-148a expression was found to be clearly downregulated in high-grade adenoma compared to low-grade adenoma on both qRT-PCR and ISH analysis. Downregulation of miR-148a expression was significantly correlated with advanced clinicopathological features and was an independent prognostic classifier in patients with stage III CRC. In CRC cells and tissues, miR-148a expression was inversely correlated with the expression of MMP7. Conclusion: We showed the collaborative participation of miR-148a and MMP7 in CRC cell invasion. These results also demonstrate that the downregulation of miR-148a expression promotes CRC progression, especially carcinogenesis and cancer cell invasion.
机译：目的：大肠癌（CRC）通过基因表达的失调和表观遗传异常的积累而发展，导致肿瘤细胞获得恶性特征。微小RNA（miRNA）在癌症发展中起着至关重要的作用，它们可以充当癌基因或抑癌药。方法：采用福尔马林固定石蜡包埋的组织样本，通过qRT-PCR检测大肠腺瘤（n = 21）和CRC（I-IV期，n = 159）患者的miR-148a表达。还进行了使用miR-148a特异性探针的原位杂交（ISH）。为了进一步证实miR-148a对CRC中的基质金属蛋白酶（MMP）7表达的直接影响，进行了MTT以及使用HT29和WiDr细胞的细胞侵袭试验。结果：在qRT-PCR和ISH分析中，与低级腺瘤相比，在高级腺瘤中发现miR-148a表达明显下调。 miR-148a表达的下调与晚期临床病理特征显着相关，并且是III期CRC患者的独立预后分类器。在CRC细胞和组织中，miR-148a的表达与MMP7的表达呈负相关。结论：我们显示了miR-148a和MMP7在CRC细胞侵袭中的协同参与。这些结果还证明，miR-148a表达的下调可促进CRC进展，尤其是癌变和癌细胞侵袭。

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