Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh 201313, India.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore.
Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188423. doi: 10.1016/j.bbcan.2020.188423. Epub 2020 Aug 29.
Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies with the lowest median and overall survival rate among all human malignancies. The major problems with the PDAC are the late diagnosis, metastasis, and acquired resistance to chemotherapeutic agents in the clinic. Over the last decade, the long non-coding RNAs (lncRNAs) have been discovered and occupies a significantly large proportion of the human genome. Recent studies have proved that lncRNAs can play a crucial role in the majority of key cellular processes involved in the maintenance of cellular homeostasis by regulating various molecular mechanisms. The deregulation of lncRNAs has been associated with various chronic diseases including human malignancies. Several lncRNAs have tumor-specific expression making them an ideal and excellent target for designing the novel therapeutic strategies against human malignancies. We have discussed how lncRNA expression can be used for the diagnosis and prognosis of PDAC. The current review discusses the potential role and molecular mechanism of lncRNA in regulating the prominent hallmarks of cancer including abnormal growth, survival, metastasis, and drug-resistance in PDAC. Importantly, we also highlight the possible application of various therapeutic strategies including small interfering RNA, CRISPR-Cas9, antisense oligonucleotides, locked nucleic acid Gapmers, small molecules, aptamers, lncRNA promoter to target the lncRNA as a novel and viable options for treatment of PDAC.
胰腺导管腺癌 (PDAC) 是致命恶性肿瘤之一,所有人类恶性肿瘤中中位生存期和总生存期最短。PDAC 的主要问题是临床诊断较晚、转移和对化疗药物的获得性耐药。在过去的十年中,长链非编码 RNA (lncRNA) 被发现并占据了人类基因组的很大比例。最近的研究证明,lncRNA 可以通过调节各种分子机制在大多数参与维持细胞内稳态的关键细胞过程中发挥关键作用。lncRNA 的失调与包括人类恶性肿瘤在内的各种慢性疾病有关。一些 lncRNA 具有肿瘤特异性表达,使其成为设计针对人类恶性肿瘤的新型治疗策略的理想和优秀靶点。我们已经讨论了 lncRNA 表达如何用于 PDAC 的诊断和预后。本综述讨论了 lncRNA 在调节 PDAC 中包括异常生长、存活、转移和耐药在内的主要癌症特征方面的潜在作用和分子机制。重要的是,我们还强调了各种治疗策略的可能应用,包括小干扰 RNA、CRISPR-Cas9、反义寡核苷酸、锁定核酸 Gapmers、小分子、适体、lncRNA 启动子来靶向 lncRNA,作为治疗 PDAC 的新的可行选择。