Wang Gang, Pan Jingen, Zhang Lu, Wei Yajun, Wang Cheng
Department of Biliary and Pancreatic Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University, Hefei, Anhui, China.
Cell Prolif. 2017 Dec;50(6). doi: 10.1111/cpr.12389. Epub 2017 Sep 21.
Colorectal neoplasia differentially expressed (CRNDE), a vital cancer-related long non-coding RNA (lncRNA), has been brought to reports for playing quintessential functions in the growth and progression of several human malignancies. Nevertheless, the expression as well as the functional mechanisms of CRNDE in pancreatic cancer is not known so for. This study aimed at investigating the biological and clinical importance of CRNDE in human pancreatic cancer.
The expression levels of CRNDE in pancreatic cancer tissues as well as cell lines were identified with the help of quantitative real-time PCR (qRT-PCR). Furthermore, the analysis of the relationship between CRNDE expression and clinicopathologic characteristics of patients with pancreatic cancer was also performed. Novel target of CRNDE was identified with the use of bioinformatics analysis and confirmed by a dual-luciferase reporter assay. Colorectal neoplasia differentially expressed was knocked down using siRNA in pancreatic cancer cells. Thereafter, cell proliferation, migration and invasion were examined. Tumour xenograft was created to explore the function of CRNDE in tumorigenesis in vivo.
Upregulation of the expression of CRNDE was found in pancreatic cancer tissues as well as cell lines, in comparison with the adjacent non-tumour tissues and human pancreatic duct epithelial cells. High expression of CRNDE was correlated with poor clinicpathological characteristics and shorter overall survival. We identified miR-384 as a direct target for CRNDE. Moreover, the CRNDE knockdown considerably inhibited pancreatic cancer cell proliferation, migration and invasion not only in vitro but also in vivo. In addition, CRNDE positively regulated IRS1 expression through sponging miR-384.
Colorectal neoplasia differentially expressed performed an oncogenic function in cell proliferation as well as metastasis of pancreatic cancer. Our results suggest that CRNDE is likely to serve as an efficient therapeutic approach in respect of pancreatic cancer treatment.
结直肠癌差异表达基因（CRNDE）是一种重要的癌症相关长链非编码RNA（lncRNA），已有报道称其在多种人类恶性肿瘤的生长和进展中发挥着重要作用。然而，CRNDE在胰腺癌中的表达及其功能机制目前尚不清楚。本研究旨在探讨CRNDE在人类胰腺癌中的生物学及临床意义。
借助定量实时PCR（qRT-PCR）鉴定胰腺癌组织及细胞系中CRNDE的表达水平。此外，还对CRNDE表达与胰腺癌患者临床病理特征之间的关系进行了分析。利用生物信息学分析鉴定CRNDE的新靶点，并通过双荧光素酶报告基因检测进行验证。使用小干扰RNA（siRNA）敲低胰腺癌细胞中的结直肠癌差异表达基因。此后，检测细胞增殖、迁移和侵袭情况。建立肿瘤异种移植模型以探究CRNDE在体内肿瘤发生中的作用。
与相邻非肿瘤组织及人胰腺导管上皮细胞相比，胰腺癌组织及细胞系中CRNDE的表达上调。CRNDE高表达与不良临床病理特征及较短的总生存期相关。我们鉴定出miR-384是CRNDE的直接靶点。此外，敲低CRNDE不仅在体外而且在体内均显著抑制胰腺癌细胞的增殖、迁移和侵袭。此外，CRNDE通过结合miR-384正向调节胰岛素受体底物1（IRS1）的表达。
结直肠癌差异表达基因在胰腺癌细胞增殖及转移中发挥致癌作用。我们的结果表明，CRNDE可能是一种有效的胰腺癌治疗方法。
