非霍奇金淋巴瘤耐药相关microRNA研究进展

Research Progress on microRNA Associated with Chemoresistance of NHL——Review

非霍奇金淋巴瘤(NHL)是起源于淋巴造血组织的恶性肿瘤,化疗是目前治疗NHL的主要手段,但化疗耐药仍旧是NHL治疗失败的重要原因。NHL多药耐药(MDR)机制复杂,涉及到多种信号通路。这些通路中的关键基因在遗传学水平的变异可以导致肿瘤细胞耐药现象的发生。microRNA是广泛存在于动物、植物及病毒中的非编码RNA,通过转录后水平调控靶基因的表达参与肿瘤细胞的分化发育及肿瘤的发生发展,其表达水平的改变在NHL的发病及耐药机制中起重要作用。因此,通过制备microRNA反义寡核苷酸(AMO),或采用microRNA替代治疗,人为地干预microRNA在NHL细胞中的表达,改变其靶向调控的相关基因蛋白的表达水平,并与NHL放化疗进行联合应用,对于逆转NHL细胞化疗耐药及放疗抵抗、改善其不良预后具有重要指导意义。本文就与NHL化疗耐药及放疗抵抗密切相关的microRNA及其潜在的作用靶点进行综述,并对这些microRNA在NHL发病及耐药机制中的具体作用进行深入阐述。

Non-Hodgkin＇s lymphoma（NHL） is a malignant tumor originated in lymphatic hematopoietic tissue.At present,chemotherapy is the main treatment method of NHL,but the chemoresistance is still an important reason for NHL treatment failure.The mechanism of NHL multidrug resistance（MDR） is complex,involving a variety of singnal pathways,in which mutation in the genetic level of the key genes can result in tumor cell resistance phenomenon.MicroRNA are small non-coding RNA that can be widely detected in plants,animal species and viruses.They regulate protein expression by repressing translation mRNA target at the post-transcriptional level,participating in the differentiation and development of tumor cells,as well as the occurrence and development of tumor,the change of the expression level microRNA plays an important role in the genesis and chemoresistance mechanism of NHL.Therefore,the intervening factitiously the expression level of microRNA in NHL through manufacturing antisense oligonucleotide （AMO） or using substitution of microRNA,changing the expression level of their target protein,and combining with the therapy of NHL,there will be an guiding significance in reversing the drug and radiation resistance of NHL,thus improving its poor prognosis.This article reviews the microRNAs closely related with drug and radiation resistance of NHL,and their potential targets.Furthermore,the specific role of these microRNAs in the genesis and chemoresistance mechanism of NHL are deeply elaborated.