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环状 RNA circ-ITCH 通过调控 miR-22 在骨肉瘤中发挥抑瘤作用。

The circular RNA circ-ITCH acts as a tumour suppressor in osteosarcoma via regulating miR-22.

机构信息

a Department of Orthopedic Oncology, The Affiliated Hospital of Qingdao University , Qingdao , Shandong , China.

b Department of Pediatrics, The Affiliated Hospital of Qingdao University , Qingdao , Shandong , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3359-3367. doi: 10.1080/21691401.2019.1649273.

DOI:10.1080/21691401.2019.1649273
PMID:31387405
Abstract

Osteosarcoma (OS) is the most prevailing primary bone tumour and the third prevalent tumour in children and adolescents. Despite advanced treatments, the survival rate of OS has not been effectively improved. Here, we intended to investigate the functional impacts of circ-ITCH on OS. Circ-ITCH expression in OS tissues and cells was evaluated utilizing qRT-PCR. Viability and proliferation of MG63 and Saos-2 cells were determined by utilizing CCK-8 assay and BrdU assay. Transwell assay was utilized to investigate migration and invasion. Western blot was utilized to distinguish apoptosis and metastasis-related proteins expression. Sequentially, the above-mentioned parameters were reassessed when up-regulating miR-22. Circ-ITCH was low expressed in OS tissues and cells. Overexpressing circ-ITCH facilitated apoptosis and repressed viability, proliferation, migration and invasion in MG63 and Saos-2 cells. MiR-22 expression was reduced by overexpressing circ-ITCH. The decline of viability, proliferation, migration and invasion made by overexpressing circ-ITCH was alleviated by up-regulating miR-22. Conclusively, circ-ITCH suppressed PTEN/PI3K/AKT and SP-1 pathways via down-regulating miR-22. Circ-ITCH took effects on apoptosis, viability, proliferation, migration and invasion through restraining PTEN/PI3K/AKT and SP-1 pathways via down-regulating miR-22 in MG63 and Saos-2 cells. Highlights Low expression of circ-ITCH is observed in osteosarcoma tissues and cell lines; Overexpression circ-ITCH suppresses miR-22 expression; Circ-ITCH promotes proliferation and represses apoptosis by up-regulating miR-22; Circ-ITCH promotes migration and invasion by up-regulating miR-22; Circ-ITCH activates PTEN/PI3K/AKT and SP-1 pathways by up-regulating miR-22.

摘要

骨肉瘤(OS)是最常见的原发性骨肿瘤,也是儿童和青少年中第三大常见肿瘤。尽管采用了先进的治疗方法,但 OS 的生存率并未得到有效提高。在这里,我们旨在研究 circ-ITCH 对 OS 的功能影响。利用 qRT-PCR 评估 OS 组织和细胞中 circ-ITCH 的表达。通过 CCK-8 测定和 BrdU 测定来确定 MG63 和 Saos-2 细胞的活力和增殖。利用 Transwell 测定来研究迁移和侵袭。利用 Western blot 来区分凋亡和转移相关蛋白的表达。然后,当上调 miR-22 时,重新评估上述参数。circ-ITCH 在 OS 组织和细胞中低表达。过表达 circ-ITCH 促进 MG63 和 Saos-2 细胞的凋亡,并抑制其活力、增殖、迁移和侵袭。circ-ITCH 过表达降低了 miR-22 的表达。上调 miR-22 缓解了过表达 circ-ITCH 导致的活力、增殖、迁移和侵袭下降。总之,circ-ITCH 通过下调 miR-22 抑制 PTEN/PI3K/AKT 和 SP-1 通路。circ-ITCH 通过下调 miR-22 通过抑制 PTEN/PI3K/AKT 和 SP-1 通路在 MG63 和 Saos-2 细胞中发挥作用,影响细胞凋亡、活力、增殖、迁移和侵袭。

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