Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-10-18 , DOI: 10.1016/j.etap.2020.103514 Yujie Tan , Hao Wang , Chan Zhang
MicroRNAs (miRNAs) have emerged as the vital post-transcriptional regulators and control the growth and progression of different cancers types. The current study aimed at exploration of the role of microRNA-381 (miRNA-381) in human cervical cancer with emphasis on the evaluation of the underlying molecular mechanism. The results revealed a significant (P < 0.05) downregulation of miRNA-381 was found in cervical cancer tissues and cancer cell lines. Overexpression of miRNA-381 in cervical cancer cells significantly (P < 0.05) inhibited their proliferation through the induction of cell apoptosis which was accompanied by depletion of Bcl-2 and increase in Bax expression. Additionally, the cleavage of caspase-3 and 9 was also activated upon miRNA-381 overexpression. The Overexpression of miRNA-381 further inhibited the migration and invasion of cervical cancer cells. In silico analysis together with dual luciferase assay revealed G protein-Coupled receptor 34 (GPR34) to be the target of miRNA-381. The expression of GPR34 was significantly (P < 0.05) upregulated in the cervical cancer tissues and cell lines. Nonetheless, miRNA-381 overexpression caused a remarkable decrease in the expression of GPR34. The GPR34 knockdown and overexpression proved that the tumor-suppressive effects of miRNA-381 are mediated via GPR34. The study elucidated the essence of miRNA-381/GPR34 molecular regulatory axis in cervical cancer and unraveled the possibility of targeting this molecular axis as an important therapeutic approach against human cervical cancer.
中文翻译:
MicroRNA-381靶向G蛋白偶联受体34(GPR34),以调节人类宫颈癌细胞的生长,迁移和侵袭
微小RNA(miRNA)已成为重要的转录后调节剂,可控制不同类型癌症的生长和进程。当前的研究旨在探索microRNA-381(miRNA-381)在人宫颈癌中的作用,重点在于对潜在分子机制的评估。结果表明,在宫颈癌组织和癌细胞系中发现了miRNA-381的显着下调(P <0.05)。宫颈癌细胞中miRNA-381的过表达显着(P <0.05)通过诱导细胞凋亡来抑制其增殖,并伴随着Bcl-2的消耗和Bax表达的增加。另外,在miRNA-381过表达后,胱天蛋白酶3和9的切割也被激活。在计算机分析和双重荧光素酶分析中发现,G蛋白偶联受体34(GPR34)是miRNA-381的靶标。在宫颈癌组织和细胞系中,GPR34的表达显着上调(P <0.05)。尽管如此,miRNA-381的过表达导致GPR34的表达显着下降。GPR34的抑制和过度表达证明miRNA-381的肿瘤抑制作用是通过GPR34介导的。这项研究阐明了miRNA-381 / GPR34分子调控轴在宫颈癌中的本质,并阐明了以该分子轴为靶标来对抗人类宫颈癌的重要治疗方法的可能性。