School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Northern Ireland, BT9 7BL, UK.
Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
BMC Cancer. 2019 Nov 21;19(1):1130. doi: 10.1186/s12885-019-6284-y.
A severe lack of early diagnosis coupled with resistance to most available therapeutic options renders pancreatic cancer as a major clinical concern. The limited efficacy of current treatments necessitates the development of novel therapeutic strategies that are based on an understanding of the molecular mechanisms involved in pancreatic cancer progression. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the expression of multiple proteins in the post-translation process and thus have promise as biomarkers, prognostic agents, and as advanced pancreatic therapies. Profiling of deregulated miRNAs in pancreatic cancer can correlate to diagnosis, indicate optimal treatment and predict response to therapy. Furthermore, understanding the main effector genes in pancreatic cancer along with downstream pathways can identify possible miRNAs as therapeutic candidates. Additionally, obstacles to the translation of miRNAs into the clinic are also considered. Distinct miRNA expression profiles can correlate to stages of malignant pancreatic disease, and hold potential as biomarkers, prognostic markers and clinical targets. However, a limited understanding and validation of the specific role of such miRNAs stunts clinical application. Target prediction using algorithms provides a wide range of possible targets, but these miRNAs still require validation through pre-clinical studies to determine the knock-on genetic effects.
早期诊断严重不足，再加上对大多数现有治疗选择的耐药性，使得胰腺癌成为一个主要的临床关注点。目前治疗方法的疗效有限，因此需要开发新的治疗策略，这些策略基于对胰腺癌进展中涉及的分子机制的理解。微小 RNA（miRNA）是一类非编码的小分子 RNA，可在翻译后过程中调节多种蛋白质的表达，因此有望作为生物标志物、预后因子和先进的胰腺癌治疗方法。对胰腺癌中失调 miRNA 的分析可以与诊断相关联，提示最佳治疗方法，并预测对治疗的反应。此外，了解胰腺癌中的主要效应基因及其下游途径可以确定可能作为治疗候选物的 miRNA。此外，还考虑了 miRNA 转化为临床应用的障碍。独特的 miRNA 表达谱与恶性胰腺疾病的阶段相关，有作为生物标志物、预后标志物和临床靶点的潜力。然而，对这些 miRNA 的具体作用的有限理解和验证阻碍了临床应用。使用算法进行靶预测提供了广泛的可能靶标，但这些 miRNA 仍需要通过临床前研究来验证，以确定遗传效应。
