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miR-23b-3p 通过降低 c-Met 表达来减少宫颈癌细胞系的增殖、迁移和侵袭。

MiR-23b-3p reduces the proliferation, migration and invasion of cervical cancer cell lines via the reduction of c-Met expression.

机构信息

Laboratorio de Investigación Clínica. Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero. Av. Lázaro Cárdenas S/N, Colonia Haciendita, Chilpancingo, 39070, Guerrero, México.

Dirección de Infecciones Crónicas y Cáncer; Centro de Investigación en Enfermedades Infecciosas. Instituto Nacional de Salud Pública. Av. Universidad No. 655, Cerrada los Pinos y Caminera. Colonia Santa María Ahuacatitlán, Cuernavaca, 62100, Morelos, México.

出版信息

Sci Rep. 2020 Feb 24;10(1):3256. doi: 10.1038/s41598-020-60143-x.

Abstract

Malignant transformation and progression in cancer is associated with the altered expression of multiple miRNAs, which are considered as post-transcriptional regulators of genes participating in various cellular processes. Although, it has been proposed that miR-23b-3p acts as a tumor suppressor in cervical cancer (CC), not all the pathways through which it alters the cellular processes have been described. The present study examines whether miR-23b-3p directly represses the c-Met expression and that consequently modifies the proliferation, migration and invasion of C33A and CaSki cells. c-Met has five microRNA response elements (MREs) for miR-23b-3p in the 3'-UTR region. The ectopic overexpression of miR-23b-3p significantly reduces c-Met expression in C33A and CaSki cells. The overexpression of miR-23b-3p reduces proliferation, migration and invasion of CaSki cells and the proliferation and invasion in C33A cells. In CaSki cells, the activation of Gab1 and Fak, downstream of c-Met, is reduced in response to the overexpression of miR-23b-3p. Together, the results in the present study indicate that miR-23b-3p is a tumor suppressor that modulates the progression of CC via post-transcriptional regulation of the c-Met oncogene.

摘要

癌症的恶性转化和进展与多种 miRNA 的表达改变有关,这些 miRNA 被认为是参与各种细胞过程的基因的转录后调节剂。虽然已经提出 miR-23b-3p 在宫颈癌 (CC) 中作为肿瘤抑制因子发挥作用,但它改变细胞过程的所有途径尚未被描述。本研究探讨了 miR-23b-3p 是否直接抑制 c-Met 的表达,从而改变 C33A 和 CaSki 细胞的增殖、迁移和侵袭。c-Met 在 3'UTR 区域有五个 miR-23b-3p 的 microRNA 反应元件 (MRE)。miR-23b-3p 的异位过表达可显著降低 C33A 和 CaSki 细胞中的 c-Met 表达。miR-23b-3p 的过表达可降低 CaSki 细胞的增殖、迁移和侵袭,以及 C33A 细胞的增殖和侵袭。在 CaSki 细胞中,c-Met 下游的 Gab1 和 Fak 的激活在 miR-23b-3p 的过表达下减少。总之,本研究的结果表明,miR-23b-3p 是一种肿瘤抑制因子,通过对 c-Met 癌基因的转录后调节来调节 CC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7273/7039958/303871930604/41598_2020_60143_Fig1_HTML.jpg

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