miR-744-5p通过靶向SOX12/Wnt/β-连环蛋白信号通路抑制多发性骨髓瘤的增殖、上皮间质转化和糖酵解。
miR-744-5p Inhibits Multiple Myeloma Proliferation, Epithelial Mesenchymal Transformation and Glycolysis by Targeting SOX12/Wnt/β-Catenin Signaling.
作者信息
Guo Bingling, Xiao Chunyan, Liu Yumin, Zhang Ning, Bai Hao, Yang Tao, Xiang Ying, Nan Yingyu, Li Qiying, Zhang Wenjun, Huang Dehong
机构信息
Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, People's Republic of China.
Medical Records Management Division, Chongqing University Cancer Hospital, Chongqing, People's Republic of China.
出版信息
Onco Targets Ther. 2021 Feb 22;14:1161-1172. doi: 10.2147/OTT.S270636. eCollection 2021.
PURPOSE
This study investigated the function and molecular mechanisms of miR-744-5p in multiple myeloma (MM).
METHODS
miR-744-5p and SRY-related high-mobility-group box 12 (SOX12) expression in clinical tissues and MM cells was monitored by quantitative real-time polymerase chain reactions and Western blot. miR-744-5p expression in MM cells was regulated by transfection. Cell proliferation was researched by cell counting kit-8 assay and plate clone formation experiment. Transwell experiment was utilized for migration and invasion detection. Glycolysis test was conducted for the detection of glucose uptake and lactate production of MM cells. The relationship between miR-744-5p and SOX12 was determined by dual-luciferase reporter gene assay and RNA pull-down experiment. In vivo experiment was conducted using nude mice.
RESULTS
miR-744-5p expression was reduced in MM patients (<0.01). Low miR-744-5p expression was associated with lower 60-month survival in MM patients (=0.0402). miR-744-5p overexpression inhibited MM cells proliferation, invasion, migration, glucose uptake, lactate production, and epithelial mesenchymal transformation (EMT) (<0.01). miR-744-5p directly inhibited SOX12 expression. miR-744-5p silencing promoted MM cells proliferation, invasion, migration, glucose uptake, lactate production, and EMT by elevating SOX12 (<0.01). miR-744-5p inhibited the growth of MM xenograft tumors in vivo (<0.001).
CONCLUSION
miR-744-5p inhibits MM cells proliferation, invasion, migration, EMT, and glycolysis by targeting SOX12/Wnt/β-catenin.
目的
本研究探讨了miR-744-5p在多发性骨髓瘤（MM）中的作用及分子机制。
方法
通过定量实时聚合酶链反应和蛋白质免疫印迹法监测临床组织和MM细胞中miR-744-5p和SRY相关高迁移率族盒12（SOX12）的表达。通过转染调节MM细胞中miR-744-5p的表达。采用细胞计数试剂盒-8法和平板克隆形成实验研究细胞增殖。利用Transwell实验检测迁移和侵袭能力。进行糖酵解试验以检测MM细胞的葡萄糖摄取和乳酸生成。通过双荧光素酶报告基因检测和RNA下拉实验确定miR-744-5p与SOX12之间的关系。使用裸鼠进行体内实验。
结果
MM患者中miR-744-5p表达降低（<0.01）。低miR-744-5p表达与MM患者较低的60个月生存率相关（=0.0402）。miR-744-5p过表达抑制MM细胞增殖、侵袭、迁移、葡萄糖摄取、乳酸生成和上皮间质转化（EMT）（<0.01）。miR-744-5p直接抑制SOX12表达。miR-744-5p沉默通过上调SOX12促进MM细胞增殖、侵袭、迁移、葡萄糖摄取、乳酸生成和EMT（<0.01）。miR-744-5p在体内抑制MM异种移植瘤的生长（<0.001）。
结论
miR-744-5p通过靶向SOX12/Wnt/β-连环蛋白抑制MM细胞增殖、侵袭、迁移、EMT和糖酵解。
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