Cao Wenlong, Wei Weiyuan, Zhan Zexu, Xie Yubo, Xiao Qiang
Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Department of Anaesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Rep. 2016 May;35(5):2583-91. doi: 10.3892/or.2016.4643. Epub 2016 Feb 29.
Routine chemotherapy as an important treatment mode often can not be effective because of multidrug resistance (MDR). MicroRNA (miRNA) modulates the expression of a great number of genes, including MDR. In this study, the expression of miR-1284 was reduced in gastric cancer (GC) tissue specimens with metastasis and in vincristine-resistant (VCR) GC SGC7901 cells (SGC-7901/VCR) compared to that in the controls. Recombinant lentiviral vectors with miR-1284 led to the overexpression of miR-1284 mRNA and reversed the chemoresistance of SGC7901/VCR cells, promoted cell cycle arrested at the G0/G1 phase, accelerated drug-induced apoptosis, and decreased migration and invasiveness of SGC-7901/VCR. In addition, the overexpression of miR-1284 sensitized tumors to chemotherapy in vivo. Our data provide combined evidence that miR-1284 can heighten the expression of MYC and reduce the expression of JUN, MMP12, and EIF4A1 that was the direct target. In conclusion, miR-1284 can function as a new regulator to reduce GC MDR cells by targeting EIF4A1.
常规化疗作为一种重要的治疗方式，常常因多药耐药（MDR）而无法发挥有效作用。微小RNA（miRNA）可调节大量基因的表达，包括与多药耐药相关的基因。在本研究中，与对照组相比，miR - 1284在伴有转移的胃癌（GC）组织标本以及长春新碱耐药（VCR）的GC SGC7901细胞（SGC - 7901/VCR）中的表达降低。携带miR - 1284的重组慢病毒载体导致miR - 1284 mRNA过表达，逆转了SGC7901/VCR细胞的化疗耐药性，促使细胞周期停滞在G0/G1期，加速药物诱导的细胞凋亡，并降低SGC - 7901/VCR的迁移和侵袭能力。此外，miR - 1284的过表达使体内肿瘤对化疗敏感。我们的数据综合表明，miR - 1284可上调MYC的表达，并降低直接靶点JUN、MMP12和EIF4A1的表达。总之，miR - 1284可作为一种新的调节因子，通过靶向EIF4A1来降低GC多药耐药细胞。
