环状 RNA CRIM1 通过靶向 miR182/Foxo3a 轴调控膀胱癌的迁移和侵袭。

circRNA CRIM1 regulates the migration and invasion of bladder cancer by targeting miR182/Foxo3a axis.

机构信息

Department of Medical Laboratory Diagnosis Center, Jinan Central Hospital, Jinan, 250013, Shandong, China.

Department of Clinical Laboratory, Zhangqiu District People's Hospital, Jinan, 250200, China.

出版信息

Clin Transl Oncol. 2022 Jun;24(6):1195-1203. doi: 10.1007/s12094-021-02768-6. Epub 2022 Jan 7.

DOI:10.1007/s12094-021-02768-6

PMID:34994952

Abstract

PURPOSE

To explore the molecular mechanism of circRNA CRIM1 in the regulation of bladder cancer by targeting the miR182/Foxo3a axis.

METHODS

50 pairs of cancer tissues and para-cancerous tissues of patients with bladder cancer were collected. RT-PCR method was used to detect the expression of CRIM1 and miR-182. The association between circRNA CRIM1 and clinical data was analyzed. qPCR was used to measure the expression of circRNA CRIM1 and miR-182 in bladder cancer cell UMUC3 and endothelial cell line HUVEC. CRIM1 genes and miR-182 in UMUC3 cell lines were overexpressed and silenced, respectively, to investigate their effects on invasion and migration of bladder cancer, and to detect the changes of miR182/Foxo3a expression. The association between circRNA CRIM1 and miR182/Foxo3a was determined by bioinformatics analysis.

RESULTS

The results showed that there was a significant association between the expression of circRNA CRIM1 and distal migration. The expression of CRIM1 in adjacent tissues was significantly down-regulated and negatively correlated with distal migration. The overexpression of circRNA CRIM1 reduced migration and invasion processes in bladder cancer cells. After circRNA CRIM1 was overexpressed, the miR-182 was significantly down-regulated. The expression levels of Foxo3a mRNA and proteins were up-regulated after miR-182 silencing of bladder cancer cell line UMUC3. miR-182 silencing inhibited invasion and migration of cancer cells to some extent. In bladder cancer cells and tissues, CRIM1 and Foxo3a were significantly down-regulated, miR-182 was significantly up-regulated.

CONCLUSION

circRNA CRIM1 regulated the migration and invasion of bladder cancer by targeting the miR182/Foxo3a axis.

摘要

目的

探讨环状 RNA CRIM1 通过靶向 miR182/Foxo3a 轴调控膀胱癌的分子机制。

方法

收集 50 对膀胱癌患者癌组织及癌旁组织，采用 RT-PCR 法检测 CRIM1 和 miR-182 的表达，分析环状 RNA CRIM1 与临床资料的相关性。qPCR 检测膀胱癌细胞 UMUC3 和血管内皮细胞系 HUVEC 中 circRNA CRIM1 和 miR-182 的表达。在 UMUC3 细胞系中转染过表达和沉默 CRIM1 基因及 miR-182，观察对膀胱癌侵袭和迁移的影响，并检测 miR182/Foxo3a 表达的变化。通过生物信息学分析确定 circRNA CRIM1 与 miR182/Foxo3a 的关系。

结果

结果显示，circRNA CRIM1 的表达与远处转移呈显著相关，癌旁组织中 CRIM1 的表达明显下调，与远处转移呈负相关。过表达 circRNA CRIM1 可降低膀胱癌细胞的迁移和侵袭过程。过表达 circRNA CRIM1 后，miR-182 表达明显下调。沉默 UMUC3 膀胱癌细胞系中的 miR-182 后，Foxo3a mRNA 和蛋白的表达水平上调。miR-182 沉默在一定程度上抑制了癌细胞的侵袭和迁移。在膀胱癌细胞和组织中，CRIM1 和 Foxo3a 的表达明显下调，miR-182 的表达明显上调。