Geng Xiaoling, Wang Haoyu, Xu Lichen, Han Yazhou, Liu Yadong
Department of Gastroenterology & Hepatology, First Affiliated Hospital of Dalian Medical University, Dalian, 116000, People's Republic of China.
Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shanxi, People's Republic of China.
Onco Targets Ther. 2021 Feb 11;14:995-1002. doi: 10.2147/OTT.S289229. eCollection 2021.
MicroRNA-140-5p plays pivotal role in different types of human malignancies, while its involvement in osteosarcoma is unknown.
Our study aimed to investigate the functionality of microRNA-140-5p in osteosarcoma.
Plasma levels of microRNA-140-5p and glucose transporter 1 (GLUT-1) in both osteosarcoma and healthy controls were measured by qRT-PCR and ELISA, respectively. Correlation between plasma levels of microRNA-140-5p and GLUT-1 was analyzed by Pearson correlation coefficient. Correlation between plasma levels of microRNA-140-5p and clinical data of patients with osteosarcoma was analyzed by Chi-square test. MicroRNA-140-5p mimic and GLUT-1 expression vector were transfected into cells of human osteosarcoma cell lines, and the effects on microRNA-140-5p expression, GLUT-1 expression and cell proliferation were analyzed by qRT-PCR, Western-blot and CCK-8 assay, respectively.
Plasma levels of microRNA-140-5p were significantly lower and plasma levels of GLUT-1 were significantly higher in osteosarcoma patients than that in healthy controls. Levels of plasma microRNA-140-5p and GLUT-1 were reversely correlated in osteosarcoma patients. Plasma levels of microRNA-140-5p were correlated with tumor size but not with other clinical data of patients. MicroRNA-140-5p mimic significantly inhibited cancer cell proliferation, while GLUT-1 overexpression significantly promoted cancer cell proliferation. MicroRNA-140-5p mimic significantly downregulated GLUT-1 expression.
GLUT-1 overexpression showed no significant effect on microRNA-140-5p expression but attenuated the inhibitory effects of microRNA-140-5p mimic on cell proliferation. We therefore conclude that microRNA-140-5p is downregulated in osteosarcoma and overexpression of microRNA-140-5p may inhibit cancer cell proliferation by downregulating GLUT-1.
微小RNA - 140 - 5p在不同类型的人类恶性肿瘤中起关键作用,但其在骨肉瘤中的作用尚不清楚。
本研究旨在探讨微小RNA - 140 - 5p在骨肉瘤中的功能。
分别采用qRT - PCR和ELISA检测骨肉瘤患者及健康对照者血浆中微小RNA - 140 - 5p和葡萄糖转运蛋白1(GLUT - 1)的水平。采用Pearson相关系数分析血浆微小RNA - 140 - 5p水平与GLUT - 1水平之间的相关性。采用卡方检验分析血浆微小RNA - 140 - 5p水平与骨肉瘤患者临床资料之间的相关性。将微小RNA - 140 - 5p模拟物和GLUT - 1表达载体转染到人骨肉瘤细胞系细胞中,分别采用qRT - PCR、Western - blot和CCK - 8法分析对微小RNA - 140 - 5p表达、GLUT - 1表达和细胞增殖的影响。
骨肉瘤患者血浆微小RNA - 140 - 5p水平显著低于健康对照者,血浆GLUT - 1水平显著高于健康对照者。骨肉瘤患者血浆微小RNA - 140 - 5p水平与GLUT - 1水平呈负相关。血浆微小RNA - 140 - 5p水平与肿瘤大小相关,但与患者的其他临床资料无关。微小RNA - 140 - 5p模拟物显著抑制癌细胞增殖,而GLUT - 1过表达显著促进癌细胞增殖。微小RNA - 140 - 5p模拟物显著下调GLUT - 1表达。
GLUT - 1过表达对微小RNA - 140 - 5p表达无显著影响,但减弱了微小RNA - 140 - 5p模拟物对细胞增殖的抑制作用。因此,我们得出结论,微小RNA - 140 - 5p在骨肉瘤中表达下调,微小RNA - 140 - 5p过表达可能通过下调GLUT - 1抑制癌细胞增殖。