环状 RNA 相互作用蛋白 1 通过 miR-34c-5p/FOSL1 轴促进鼻咽癌的进展。

CircCRIM1 promotes nasopharyngeal carcinoma progression via the miR-34c-5p/FOSL1 axis.

机构信息

Oncology Department, The Second People's Hospital of Hunan Province, Changsha, 410007, Hunan, People's Republic of China.

Oncology Department, Affiliated Nanhua Hospital of University of South China, No. 336 Dong Feng South Road, Hengyang, 421002, Hunan, People's Republic of China.

出版信息

Eur J Med Res. 2022 Apr 28;27(1):59. doi: 10.1186/s40001-022-00667-2.

BACKGROUND

Nasopharyngeal carcinoma (NPC) is a rare malignancy with multiple risk factors (Epstein-Barr virus, etc.) that seriously threatens the health of people. CircRNAs are known to regulate the tumorigenesis of malignant tumours, including NPC. Moreover, circCRIM1 expression is reported to be upregulated in NPC. Nevertheless, the impact of circCRIM1 on NPC progression is not clear.

METHODS

An MTT assay was performed to assess cell viability. In addition, cell invasion and migration were assessed by the transwell assay. Dual luciferase assays were performed to assess the association among circCRIM1, miR-34c-5p and FOSL1. Moreover, RT-qPCR was applied to assess mRNA levels, and protein levels were determined by Western blot.

RESULTS

CircCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated. Knockdown of circCRIM1 significantly decreased the invasion, viability and migration of NPC cells. The miR-34c-5p inhibitor notably promoted the malignant behaviour of NPC cells, while miR-34c-5p mimics exerted the opposite effect. Moreover, circCRIM1 could bind with miR-34c-5p, and FOSL1 was identified to be downstream of miR-34c-5p. Furthermore, circCRIM1 downregulation notably inhibited the proliferation and invasion of NPC cells, while this phenomenon was significantly reversed by FOSL1 overexpression.

CONCLUSION

Silencing circCRIM1 inhibited the tumorigenesis of NPC. Thus, circCRIM1 might be a novel target for NPC.

背景

鼻咽癌（NPC）是一种罕见的恶性肿瘤，具有多种危险因素（EB 病毒等），严重威胁着人们的健康。circRNAs 被认为可以调节包括 NPC 在内的恶性肿瘤的肿瘤发生。此外，已有报道称 circCRIM1 在 NPC 中表达上调。然而，circCRIM1 对 NPC 进展的影响尚不清楚。

方法

通过 MTT 法评估细胞活力。此外，通过 Transwell 测定法评估细胞侵袭和迁移。通过双荧光素酶报告基因实验评估 circCRIM1、miR-34c-5p 和 FOSL1 之间的关联。此外，通过 RT-qPCR 评估 mRNA 水平，通过 Western blot 确定蛋白水平。

结果

circCRIM1 和 FOSL1 在 NPC 细胞中上调，而 miR-34c-5p 下调。circCRIM1 的敲低显著降低了 NPC 细胞的侵袭、活力和迁移。miR-34c-5p 抑制剂显著促进了 NPC 细胞的恶性行为，而 miR-34c-5p 模拟物则产生相反的效果。此外，circCRIM1 可以与 miR-34c-5p 结合，并且 FOSL1 被鉴定为 miR-34c-5p 的下游靶点。此外，circCRIM1 的下调显著抑制了 NPC 细胞的增殖和侵袭，而 FOSL1 的过表达显著逆转了这一现象。