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非编码RNA在促进和支持结直肠癌化疗耐药中的机制作用

The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer.

作者信息

Micallef Isaac, Baron Byron

机构信息

Centre for Molecular Medicine and Biobanking, University of Malta, MSD2080 Msida, Malta.

出版信息

Noncoding RNA. 2021 Mar 31;7(2):24. doi: 10.3390/ncrna7020024.

Abstract

Colorectal Cancer (CRC) is one of the most common gastrointestinal malignancies which has quite a high mortality rate. Despite the advances made in CRC treatment, effective therapy is still quite challenging, particularly due to resistance arising throughout the treatment regimen. Several studies have been carried out to identify CRC chemoresistance mechanisms, with research showing different signalling pathways, certain ATP binding cassette (ABC) transporters and epithelial mesenchymal transition (EMT), among others to be responsible for the failure of CRC chemotherapies. In the last decade, it has become increasingly evident that certain non-coding RNA (ncRNA) families are involved in chemoresistance. Research investigations have demonstrated that dysregulation of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute towards promoting resistance in CRC via different mechanisms. Considering the currently available data on this phenomenon, a better understanding of how these ncRNAs participate in chemoresistance can lead to suitable solutions to overcome this problem in CRC. This review will first focus on discussing the different mechanisms of CRC resistance identified so far. The focus will then shift onto the roles of miRNAs, lncRNAs and circRNAs in promoting 5-fluorouracil (5-FU), oxaliplatin (OXA), cisplatin and doxorubicin (DOX) resistance in CRC, specifically using ncRNAs which have been recently identified and validated under in vivo or in vitro conditions.

摘要

结直肠癌(CRC)是最常见的胃肠道恶性肿瘤之一,死亡率相当高。尽管CRC治疗取得了进展,但有效的治疗仍然颇具挑战性,特别是由于整个治疗过程中出现的耐药性。已经开展了多项研究来确定CRC的化疗耐药机制,研究表明不同的信号通路、某些ATP结合盒(ABC)转运蛋白和上皮间质转化(EMT)等是CRC化疗失败的原因。在过去十年中,越来越明显的是某些非编码RNA(ncRNA)家族参与了化疗耐药。研究调查表明,微小RNA(miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA)的失调通过不同机制促进CRC的耐药性。考虑到目前关于这一现象的可用数据,更好地了解这些ncRNA如何参与化疗耐药可以为克服CRC中的这一问题带来合适的解决方案。本综述将首先重点讨论迄今为止确定的CRC耐药的不同机制。然后重点将转向miRNA、lncRNA和circRNA在促进CRC对5-氟尿嘧啶(5-FU)、奥沙利铂(OXA)、顺铂和阿霉素(DOX)耐药中的作用,特别是使用最近在体内或体外条件下鉴定和验证的ncRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1546/8103280/57bea37babd2/ncrna-07-00024-g001.jpg

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