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MicroRNA-532-3p Suppresses Malignant Behaviors of Tongue Squamous Cell Carcinoma via Regulating CCR7

机译:MicroRNA-532-3p通过调节CCR7抑制舌鳞状细胞癌的恶性行为。

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摘要

To provide better therapeutic avenues for treating tongue squamous cell carcinoma (TSCC), a series of experiments about the effects of microRNA (miR)-532-3p on TSCC malignant behaviors were carried out. The result showed that miR-532-3p was down-regulated and C-C chemokine receptor 7 (CCR7) was up-regulated in the tumor tissues compared with those in the paired paratumor tissues. Further, expression of miR-532-3p was detected in four TSCC cell lines, TSCCA, TCA8113, CAL-27, and SCC-25. The miR-532-3p mimics and inhibitor were transfected into the CAL-27 and TCA8113 cell lines which were the relatively lowest and highest miR-532-3p expressions, respectively. It was found that the overexpression of miR-532-3p suppressed TSCC cell proliferation, migration, invasion, and promoted apoptosis in vitro, whilst the knockdown of miR-532-3p reversed these behaviors. The bioinformatics predicted that CCR7 was a downstream gene of miR-532-3p, which was confirmed via luciferase assay. Following, the decline of CCR7 in the miR-532-3p mimics group and the rise of CCR7 in the miR-532-3p inhibitor group were also verified. In addition, enhanced cell proliferation, migration and invasion induced by CCR7 were partly restrained by miR-532-3p in TSCC cell. Meanwhile, miR-532-3p attenuated tumourigenesis in vivo due to the reduction of tumor volume and Ki-67 positive rate and the increase of apoptotic cells. Taken together, these findings reveal a pivotal role for the miR-532-3p/CCR7 axis in regulating TSCC, and this novel axis could be suitable for therapeutic intervention in TSCC disease.
机译:为了提供更好的治疗舌鳞状细胞癌(TSCC)的方法,进行了一系列有关microRNA(miR)-532-3p对TSCC恶性行为影响的实验。结果表明,与成对的癌旁组织相比,肿瘤组织中的miR-532-3p被下调,C-C趋化因子受体7(CCR7)被上调。此外,在四个TSCC细胞系TSCCA,TCA8113,CAL-27和SCC-25中检测到miR-532-3p的表达。将miR-532-3p模拟物和抑制剂转染到CAL-27和TCA8113细胞系中,它们分别是相对最低和最高的miR-532-3p表达。发现miR-532-3p的过表达抑制了体外TSCC细胞的增殖,迁移,侵袭并促进了细胞凋亡,而敲低miR-532-3p则逆转了这些行为。生物信息学预测,CCR7是miR-532-3p的下游基因,这已通过荧光素酶测定得到证实。随后,还验证了miR-532-3p模拟组中CCR7的下降和miR-532-3p抑制剂组中CCR7的上升。此外,miR-532-3p在TSCC细胞中部分抑制了CCR7诱导的细胞增殖,迁移和侵袭。同时,由于肿瘤体积和Ki-67阳性率的降低以及凋亡细胞的增加,miR-532-3p在体内减弱了肿瘤的发生。综上所述,这些发现揭示了miR-532-3p / CCR7轴在调节TSCC中的关键作用,而这一新颖的轴可能适用于TSCC疾病的治疗干预。

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