Shams Roshanak, Asadzadeh Aghdaei Hamid, Behmanesh Ali, Sadeghi Amir, Zali Mohammadareza, Salari Sina, Padrón José M
Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Student Research Committee, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran.
Cancer Manag Res. 2020 Apr 1;12:2393-2404. doi: 10.2147/CMAR.S245872. eCollection 2020.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and a major health problem worldwide. There were no major advances in conventional treatments in inhibiting tumor progression and increasing patient survival time. In order to suppress mechanisms responsible for tumor cell development such as those with oncogenic roles, more advanced therapeutic strategies should be sought. One of the most important oncogenes of pancreatic cancer is the gene. The overexpression of can activate many tumorigenic processes such as cell proliferation and pancreatic cancer cell invasion. MiRNAs are important molecules that are confirmed by targeting mRNA transcripts to regulate the expression of the gene. Therefore, restoring -repressing miRNAs expression tends to be an effective method of treating MYC-driven cancers.
The purpose of this study was to identify all validated microRNAs targeting expression to inhibit PDAC progression by conducting a systematic review.
In this systematic review study, the papers published between 2000 and 2020 in major online scientific databases including PubMed, Scopus, and Web of Science were screened, following inclusion and exclusion criteria. We extracted all the experimental studies that showed miRNAs could target the expression of the MYC gene in PDAC.
Eight papers were selected from a total of 89 papers. We found that six miRNAs (Let-7a, miR-145, miR-34a, miR-375, miR-494, and miR-148a) among the selected studies were validated for targeting MYC gene and three of them confirmed Let-7a as a direct MYC expression regulator in PC cells. Finally, we summarized the latest shreds of evidence of experimentally validated miRNAs targeting the MYC gene with respect to PDAC's therapeutic potential.
Restoring the expression of -repressing miRNAs tends to be an effective way to treat -driven cancers such as PDAC. Several miRNAs have been proposed to target this oncogene via bioinformatics tools, but only a few have been experimentally validated for pancreatic cancer cells and models. Further studies should be conducted to find the interaction network of miRNA- to develop more successful therapeutic strategies for PC, using the synergistic effects of these miRNAs.
胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，也是全球主要的健康问题。传统治疗在抑制肿瘤进展和延长患者生存时间方面没有重大进展。为了抑制负责肿瘤细胞发展的机制，如那些具有致癌作用的机制，应寻求更先进的治疗策略。胰腺癌最重要的致癌基因之一是MYC基因。MYC的过表达可激活许多致癌过程，如细胞增殖和胰腺癌细胞侵袭。微小RNA（miRNA）是通过靶向mRNA转录本来调节MYC基因表达而被证实的重要分子。因此，恢复抑制MYC的miRNA表达往往是治疗MYC驱动癌症的有效方法。
本研究的目的是通过系统评价来确定所有已验证的靶向MYC表达以抑制PDAC进展的微小RNA。
在这项系统评价研究中，按照纳入和排除标准，筛选了2000年至2020年在包括PubMed、Scopus和Web of Science在内的主要在线科学数据库中发表的论文。我们提取了所有显示miRNA可靶向PDAC中MYC基因表达的实验研究。
从总共89篇论文中选出8篇。我们发现，所选研究中的6种miRNA（Let-7a、miR-145、miR-34a、miR-375、miR-494和miR-148a）被证实可靶向MYC基因，其中3种证实Let-7a是胰腺癌细胞中MYC表达的直接调节因子。最后，我们总结了关于靶向MYC基因的经实验验证的miRNA在PDAC治疗潜力方面的最新证据。
恢复抑制MYC的miRNA表达往往是治疗MYC驱动的癌症（如PDAC）的有效方法。通过生物信息学工具已提出几种miRNA靶向该致癌基因，但只有少数在胰腺癌细胞和模型中得到实验验证。应进行进一步研究以发现miRNA-MYC的相互作用网络，利用这些miRNA的协同作用为胰腺癌开发更成功的治疗策略。
