Department of Oncology, Shanghai Tenths People's Hospital, Tongji University, Shanghai, China.
Tongji University Cancer Center, Shanghai, China.
J Cell Physiol. 2019 May;234(5):6746-6757. doi: 10.1002/jcp.27421. Epub 2018 Nov 1.
Recent evidence has highlighted that long noncoding RNAs (lncRNA) are associated with many diseases, particularly cancer. However, current understanding of the lncRNA deleted in lymphocytic leukemia 1 (DLEU1) in pancreatic ductal adenocarcinoma (PDAC) remains limited. Our studies indicated that the DLEU1 expression level was upregulated in PDAC tissue samples compared with adjacent normal tissue. Moreover, the aberrant overexpression of DLEU1 indicated poor prognosis of patients with PDAC. Loss-of-function experiments revealed that DLEU1 knockdown inhibited the proliferation, migration, and invasion of PDAC cells in vitro and decreased tumor growth in vivo. Bioinformatics analysis predicted that miR-381 potentially targeted the DLEU1 3'-untranslated region (UTR), suggesting an interaction between miR-381 and DLEU1. Furthermore, miR-381 also targeted the chemokine receptor-4 (CXCR4) messenger RNA 3'-UTR, which was validated by luciferase reporter assay. Taken together, our study demonstrated the oncogenic role of DLEU1 in clinical PDAC specimens and cellular experiments, showing the potential involvement of DLEU1/miR-381/CXCR4 pathway. These results provide novel insight into PDAC tumorigenesis.
最近的证据表明,长非编码 RNA(lncRNA)与许多疾病有关,特别是癌症。然而,目前对胰腺导管腺癌(PDAC)中缺失的淋巴细胞白血病 1(DLEU1)lncRNA 的了解仍然有限。我们的研究表明,与相邻正常组织相比,PDAC 组织样本中的 DLEU1 表达水平上调。此外,DLEU1 的异常过表达表明 PDAC 患者的预后不良。功能丧失实验表明,DLEU1 敲低抑制了 PDAC 细胞在体外的增殖、迁移和侵袭,并减少了体内肿瘤的生长。生物信息学分析预测 miR-381 可能靶向 DLEU1 的 3'-非翻译区(UTR),提示 miR-381 和 DLEU1 之间存在相互作用。此外,miR-381 还靶向趋化因子受体-4(CXCR4)信使 RNA 的 3'-UTR,这通过荧光素酶报告基因实验得到了验证。总之,我们的研究表明 DLEU1 在临床 PDAC 标本和细胞实验中具有致癌作用,表明 DLEU1/miR-381/CXCR4 通路可能参与其中。这些结果为 PDAC 肿瘤发生提供了新的见解。