Department of Obstetrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, 471009, China.
Department of Obstetrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, 471009, China.
Environ Toxicol Pharmacol. 2021 Jan;81:103514. doi: 10.1016/j.etap.2020.103514. Epub 2020 Oct 18.
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.
微小 RNA(miRNAs)已成为重要的转录后调控因子,控制着不同癌症类型的生长和进展。本研究旨在探索微小 RNA-381(miRNA-381)在人宫颈癌中的作用,重点评估其潜在的分子机制。结果显示,miRNA-381 在宫颈癌组织和癌细胞系中表达显著下调(P<0.05)。在宫颈癌细胞中过表达 miRNA-381 可通过诱导细胞凋亡显著抑制其增殖(P<0.05),伴随 Bcl-2 耗竭和 Bax 表达增加。此外,过表达 miRNA-381 还可激活 caspase-3 和 9 的裂解。miRNA-381 的过表达进一步抑制了宫颈癌细胞的迁移和侵袭。计算机分析和双荧光素酶报告基因实验表明 G 蛋白偶联受体 34(GPR34)是 miRNA-381 的靶基因。GPR34 在宫颈癌组织和细胞系中的表达显著上调(P<0.05)。然而,miRNA-381 的过表达导致 GPR34 表达显著降低。GPR34 的敲低和过表达证明了 miRNA-381 的肿瘤抑制作用是通过 GPR34 介导的。该研究阐明了 miRNA-381/GPR34 分子调控轴在宫颈癌中的本质,并揭示了靶向该分子轴作为治疗人宫颈癌的重要方法的可能性。