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环状 RNA circ_0067934 通过海绵吸附 miR-1304 和调节 CXCR1 表达促进甲状腺癌细胞凋亡,抑制细胞增殖、迁移和侵袭。

Circular RNA circ_0067934 exhaustion expedites cell apoptosis and represses cell proliferation, migration and invasion in thyroid cancer via sponging miR-1304 and regulating CXCR1 expression.

机构信息

Department of Thyroid Breast Surgery, Anhui Provincial Hospital, Hefei, Anhui, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Dec;23(24):10851-10866. doi: 10.26355/eurrev_201912_19789.

DOI:10.26355/eurrev_201912_19789
PMID:31858554
Abstract

OBJECTIVE

Distant metastasis or local recurrence is the leading cause of death in some patients with thyroid cancer (TC), a malignant tumor of the endocrine system. Circular RNA circ_0067934 (circ_0067934) has been reported to be connected with the tumorigenesis of multiple tumors. However, there are few reports on the role and regulatory mechanisms of circ_0067934 in TC.

MATERIALS AND METHODS

The expression levels of circ_0067934, protein kinase C iota (PRKCI), microRNA-1304 (miR-1304), and C-X-C chemokine receptor types 1 (CXCR1) were detected with quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The proliferation, apoptosis, migration, and invasion of TC cells were evaluated by Cell Counting Kit-8 (CCK8) assay, flow cytometry assay, and transwell assay, respectively. The relationship between circ_0067934 or CXCR1 and miR-1304 was confirmed with Dual-Luciferase reporter assay or RNA immunoprecipitation (RIP) assay. Protein level of CXCR1 was analyzed via Western blot analysis. Xenograft assay was executed to verify the role of circ_0067934 in vivo.

RESULTS

Circ_0067934 and CXCR1 were enhanced and miR-1304 decreased in TC tissues and cells. Circ_0067934 downregulation triggered apoptosis and curbed proliferation, migration, and invasion of TC cells in vitro, as well as repressed tumor growth in vivo. Notably, circ_0067934 regulated CXCR1 expression via sponging miR-1304 in TC cells. Both miR-1304 silencing and CXCR1 elevation reversed the facilitation of apoptosis and the retardation of proliferation, migration, and invasion induced by circ_0067934 reduction in TC cells.

CONCLUSIONS

Circ_0067934 downregulation expedited apoptosis and retarded proliferation, migration, and invasion of TC cells through miR-1304/CXCR1 axis.

摘要

目的

远处转移或局部复发是内分泌系统恶性肿瘤甲状腺癌(TC)患者死亡的主要原因。环状 RNA circ_0067934(circ_0067934)已被报道与多种肿瘤的发生有关。然而,关于 circ_0067934 在 TC 中的作用及其调控机制的报道较少。

材料与方法

采用实时荧光定量聚合酶链反应(qRT-PCR)检测 circ_0067934、蛋白激酶 C iota(PRKCI)、微小 RNA-1304(miR-1304)和 C-X-C 趋化因子受体 1(CXCR1)的表达水平。通过细胞计数试剂盒-8(CCK8)检测、流式细胞术检测和 Transwell 检测分别评估 TC 细胞的增殖、凋亡、迁移和侵袭。通过双荧光素酶报告基因检测或 RNA 免疫沉淀(RIP)检测证实 circ_0067934 或 CXCR1 与 miR-1304 的关系。通过 Western blot 分析检测 CXCR1 蛋白水平。进行异种移植实验以验证 circ_0067934 在体内的作用。

结果

TC 组织和细胞中 circ_0067934 和 CXCR1 上调,miR-1304 下调。circ_0067934 下调可触发 TC 细胞凋亡并抑制体外增殖、迁移和侵袭,同时抑制体内肿瘤生长。值得注意的是,circ_0067934 通过海绵吸附 miR-1304 调控 TC 细胞中的 CXCR1 表达。miR-1304 沉默和 CXCR1 上调均可逆转 circ_0067934 下调诱导的 TC 细胞凋亡促进和增殖、迁移和侵袭抑制。

结论

circ_0067934 下调通过 miR-1304/CXCR1 轴加速 TC 细胞凋亡并抑制增殖、迁移和侵袭。

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