MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients.

中文翻译：

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MicroRNA-466（miR-466）在大肠癌（CRC）中起着抑癌和预后的作用。

微小RNA（miRNA）在调节肿瘤的发展和转移中具有重要作用。在这项研究中，我们调查了miR-466在结直肠癌（CRC）中的临床和预后价值以及生物学功能。从诊断为CRC的100例患者中获得肿瘤和邻近的健康组织。通过定量逆转录聚合酶链反应（qRT-PCR）确定miR-466的表达。通过qRT-PCR和Western blot分别在转染了miR-466拟南芥或siRNA的SW-620 CRC细胞中分析了细胞周期蛋白D1，凋亡调节剂BAX（BAX）和基质金属蛋白酶2（MMP-2）的mRNA和蛋白水平。阴性对照miRNA。使用CCK-8检测，流式细胞术和Transwell检测分别研究了miR-466对SW-620细胞增殖，细胞周期和凋亡以及侵袭的影响。与匹配的相邻非肿瘤组织相比，miR-466表达在肿瘤组织中显着下调。miR-466的低表达与肿瘤大小，肿瘤淋巴结转移阶段，淋巴结转移和远处转移密切相关。与高miR-466表达组相比，低miR-466表达的CRC患者的总生存期明显缩短（对数秩检验：p = 0.0103）。多变量分析显示，miR-466低表达与CRC患者的预后不良有关。miR-466的异位表达抑制SW-620细胞中的细胞增殖和迁移/侵袭，并诱导G0 / G1阻滞和凋亡。此外，miR-466的异位表达降低了cyclin D1和MMP-2的表达，但增加了SW-620细胞中的BAX表达。结论，