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hsa_circ_0041103 通过 miR-107/FOXK1 轴诱导膀胱癌的增殖、迁移和侵袭。

Hsa_circ_0041103 induces proliferation, migration and invasion in bladder cancer via the miR-107/FOXK1 axis.

机构信息

Department of Urology Surgery, Huaibei People's Hospital, Huaibei, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1282-1290. doi: 10.26355/eurrev_202102_24832.

Abstract

OBJECTIVE

CircRNAs have been proven to be vital during the process of malignant tumors. Their functions in bladder cancer (BCa) process remain largely unclear. This study aims to elucidate the role of circ0041103 in affecting the malignant phenotypes of BCa, and the possible molecular mechanism.

PATIENTS AND METHODS

Circ0041103 expression levels in BCa tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The clinical significance of circ0041103 in influencing tumor size, tumor staging and lymphatic metastasis of BCa was analyzed. Regulatory effects of circ0041103 on proliferative and metastatic capacities of T24 and UM-UC-3 cells were examined through functional experiments. The binding target of circ0041103 and its downstream protein were predicted by online bioinformatic tools, which were further confirmed by Dual-Luciferase reporter assay and Pearson correlation test. The role of circ0041103/miR-107/ FOXK1 axis in regulating BCa process was explored by rescue experiments.

RESULTS

Circ0041103 was abnormally upregulated in BCa tissues and cell lines. Its level was higher in BCa tissues with a larger tumor size, or worse tumor staging, or BCa cases with lymphatic metastasis. Knockdown of circ0041103 inhibited proliferative and metastatic capacities of T24 and UM-UC-3 cells. MiR-107 was the binding target of circ0041103, and FOXK1 was the downstream gene of miR-107. Overexpression of circ0041103 could reverse the inhibited proliferative and metastatic capacities of T24 and UM-UC-3 cells overexpressing miR-107.

CONCLUSIONS

Circ0041103 is upregulated in BCa and predicts a poor prognosis in BCa. It stimulates BCa cells to proliferate and migrate via the miR-107/FOXK1 axis.

摘要

目的

circRNAs 在恶性肿瘤的发生过程中被证明是至关重要的。它们在膀胱癌(BCa)过程中的作用在很大程度上尚不清楚。本研究旨在阐明 circ0041103 影响 BCa 恶性表型的作用及其可能的分子机制。

患者和方法

通过实时定量聚合酶链反应(qRT-PCR)检测 BCa 组织和细胞系中 circ0041103 的表达水平。分析 circ0041103 对 BCa 肿瘤大小、肿瘤分期和淋巴转移的影响的临床意义。通过功能实验检测 circ0041103 对 T24 和 UM-UC-3 细胞增殖和转移能力的调节作用。通过在线生物信息学工具预测 circ0041103 的结合靶标及其下游蛋白,进一步通过双荧光素酶报告基因检测和 Pearson 相关性检验进行验证。通过 rescue 实验探讨 circ0041103/miR-107/FOXK1 轴在调节 BCa 过程中的作用。

结果

circ0041103 在 BCa 组织和细胞系中异常上调。在肿瘤较大、肿瘤分期较差或有淋巴转移的 BCa 组织中,circ0041103 的水平较高。circ0041103 敲低抑制了 T24 和 UM-UC-3 细胞的增殖和转移能力。miR-107 是 circ0041103 的结合靶标,FOXK1 是 miR-107 的下游基因。circ0041103 的过表达可以逆转过表达 miR-107 的 T24 和 UM-UC-3 细胞增殖和转移能力的抑制。

结论

circ0041103 在 BCa 中上调,并预测 BCa 的预后不良。它通过 miR-107/FOXK1 轴刺激 BCa 细胞增殖和迁移。

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