Department of General Surgery, The people's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, No. 2, Xinmin RD, Danyang 212300, Jiangsu Province, China.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20200010.
As one of the most prevalent malignant tumors, pancreatic cancer (PC) is a leading fatal cancer worldwide. Surging evidence has unraveled that miRNAs are involved in the occurrence and progression of multiple cancers, including PC. The tumor suppressor effects of miR-4269 have been certified in gastric carcinoma. However, the potential function of miR-4269 remains largely unclear, which drives us to identify the role of miR-4269 in PC development. In the present study, we determined the expression pattern of miR-4269 in PC cells and normal cells. Results of RT-qPCR analysis illuminated that miR-4269 expression level in PC cells was lower than that in normal cells. Functional assays demonstrated that up-regulation of miR-4269 obviously inhibited the proliferation, migration and invasion of PC cells. In order to elucidate the mechanism governing miR-4269 in PC, we carried out bioinformatics analysis and further experimental investigations. Our results validated that ZEB1 was a direct target of miR-4269. Additionally, ZEB1 activated the transcription of OXT1. More importantly, miR-4269 attenuated the expression level of OXT1 via targeting ZEB1. Ultimately, our findings confirmed that miR-4269 served as a cancer suppressor in PC through regulation of ZEB1/OTX1 pathway, which suggested that miR-4269 might represent a promising target for the clinical treatment of PC.
作为最常见的恶性肿瘤之一，胰腺癌（PC）是全球主要的致命癌症。越来越多的证据表明，miRNA 参与了多种癌症的发生和发展，包括 PC。miR-4269 在胃癌中的肿瘤抑制作用已得到证实。然而，miR-4269 的潜在功能在很大程度上仍不清楚，这促使我们确定 miR-4269 在 PC 发展中的作用。在本研究中，我们确定了 miR-4269 在 PC 细胞和正常细胞中的表达模式。RT-qPCR 分析结果表明，PC 细胞中 miR-4269 的表达水平低于正常细胞。功能测定表明，miR-4269 的上调明显抑制了 PC 细胞的增殖、迁移和侵袭。为了阐明 miR-4269 在 PC 中的调控机制，我们进行了生物信息学分析和进一步的实验研究。我们的结果验证了 ZEB1 是 miR-4269 的直接靶标。此外，ZEB1 激活了 OXT1 的转录。更重要的是，miR-4269 通过靶向 ZEB1 减弱了 OXT1 的表达水平。最终，我们的研究结果证实，miR-4269 通过调节 ZEB1/OTX1 通路在 PC 中发挥肿瘤抑制作用，这表明 miR-4269 可能成为 PC 临床治疗的有前途的靶点。
