Yong Sun, Yabin Yu, Bing Zhou, Chuanrong Zhu, Dianhua Gu, Jianhuai Zhang, Weidong Yuan, Shuming Wang, Ling Liu
Department of Hepatobiliary and Pancreatic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, People's Republic of China.
Oncotarget. 2017 Jun 6;8(53):90868-90878. doi: 10.18632/oncotarget.18377. eCollection 2017 Oct 31.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Long non-coding microRNAs (lncRNAs) are a newly discovered type of regulatory molecule with both diagnostic and prognostic value, but the role of lncRNA in PDAC has not been well investigated until now. Here, we present evidence that shows that the lncRNA DGCR5 is significantly reduced in PDAC tissues as well as in PDAC cell lines and that the downregulation of DGCR5 predicts poor prognosis. Ectopic expression of DGCR5 inhibits the proliferation and migration, and promotes 5-FU resistances of PDAC cells. Further experiments demonstrated that DGCR5 and miR-320a regulate each other in a reciprocal manner and that DGCR5 reverses the inhibition of PDCD4 by miR-320a, which is involved in the regulation of the PDAC cell phenotype and response to 5-FU. Our findings provide novel information about the functions of lncRNAs in PDAC, some of which might be beneficial to the precise diagnosis, prognosis and individualized therapy of patients with PDAC in the future.
胰腺导管腺癌(PDAC)是最具侵袭性和致命性的恶性肿瘤之一。长链非编码微小RNA(lncRNAs)是一类新发现的具有诊断和预后价值的调控分子,但迄今为止lncRNA在PDAC中的作用尚未得到充分研究。在此,我们提供的证据表明,lncRNA DGCR5在PDAC组织以及PDAC细胞系中显著降低,且DGCR5的下调预示着预后不良。DGCR5的异位表达抑制了PDAC细胞的增殖和迁移,并增强了其对5-氟尿嘧啶(5-FU)的耐药性。进一步的实验表明,DGCR5和miR-320a以相互作用的方式相互调节,且DGCR5可逆转miR-320a对PDCD4的抑制作用,这与PDAC细胞表型的调控及对5-FU的反应有关。我们的研究结果提供了关于lncRNAs在PDAC中功能的新信息,其中一些信息可能有助于未来对PDAC患者进行精确诊断、预后评估及个体化治疗。