Circ_0017274 acts on miR-637/CDX2 axis to facilitate cisplatin resistance in gastric cancer

被引:11
作者
Xu, Bing [1 ]
Guo, Jinjuan [2 ]
Chen, Mei [3 ]
机构
[1] First Peoples Hosp Lianyungang, Dept Pharm, Lianyungang, Peoples R China
[2] Nanjing Med Univ, Kangda Coll, Affiliated Hosp 1, Dept Pharm, Lianyungang, Peoples R China
[3] First Peoples Hosp Lianyungang, Med Insurance Div, 6 East Zhenhua Rd, Lianyungang 222061, Peoples R China
关键词
CDDP; CDX2; circ_0017274; gastric cancer; miR-637; CIRCULAR RNA; MULTIDRUG-RESISTANCE; CDX2; CELLS; EXPRESSION; EPIDEMIOLOGY; SENSITIVITY; BIOMARKER; BRCA1;
D O I
10.1111/1440-1681.13692
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Currently, a substantial amount of circular RNAs (circRNAs) are closely associated with cancer development and the occurrence of drug resistance, however, circ_0017274 in cisplatin (CDDP) resistance in gastric cancer (GC) has not been addressed. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were utilized for circ_0017274, microRNA-637 (miR-637) and caudal-related homeobox transcription factor 2 (CDX2) contents analysis. Analysis of IC50, proliferation, cell cycle, apoptosis, migration and invasion of GC cells using Cell Counting Kit-8 (CCK8), 5-ethynyl-2 '-deoxyuridine (EdU), flow cytometry or transwell assays. Interaction between miR-637 and circ_0017274 or CDX2 was validated under the application of luciferase reporter system, RNA immunoprecipitation (RIP) analysis, and pull-down assay. The effect of circ_0017274 on CDDP sensitivity in vivo was tapped by xenograft models. Circ_0017274 and CDX2 had higher content in CDDP-resistant GC tissues and cells, while miR-637 had lower content. CDDP resistance and development of GC cells were arrested when circ_0017274 level was reduced in vitro. MiR-637 acted as a target of circ_0017274, and miR-637 downregulation abated the phenomenon of elevated sensitivity of sh-circ_0017274 to CDDP. MiR-637 was also demonstrated to interact with CDX2 and to co-regulate CDDP sensitivity in GC cells. The xenograft models also established that circ_0017274 downregulation strengthened CDDP sensitivity and thus curtailed tumour growth in vivo. Circ_0017274 downregulation boosted CDDP sensitivity by acting on miR-637/CDX2 in CDDP-resistant GC cells.
引用
收藏
页码:1105 / 1115
页数:11
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