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Circ_SNX27 通过 miR-637/FGFR1 轴调控肝细胞癌的发展。

Circ_SNX27 regulates hepatocellular carcinoma development via miR-637/FGFR1 axis.

机构信息

Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Environ Toxicol. 2022 Dec;37(12):2832-2843. doi: 10.1002/tox.23640. Epub 2022 Aug 27.

DOI:10.1002/tox.23640
PMID:36029209
Abstract

BACKGROUND

Circular RNAs (circRNAs) serve as critical regulatory factors in cancer development. Nonetheless, the potential regulatory mechanism of circRNA sorting nexin 27 (circ_SNX27) in hepatocellular carcinoma (HCC) is still unknown.

METHODS

The circ_SNX27, microRNA-637 (miR-637), and fibroblast growth factor receptor 1 (FGFR1) levels were quantified by quantitative real-time polymerase chain reaction and western blot analysis. Next, function experiments were conducted using in vitro assays and in vivo senograft study. The relationship between miR-637 with circ_SNX27 or FGFR1 was uncovered by dual-luciferase reporter and RNA pull-down assays.

RESULTS

The circ_SNX27 and FGFR1 levels were up-regulated, but miR-637 content was reduced in HCC. Circ_SNX27 down-regulation inhibited HCC cell proliferation, motility, and invasion and promoted apoptosis in vitro, as well as weakened tumor growth in vivo. Circ_SNX27 served as a sponge of miR-637 to promote FGFR1 expression. MiR-637 reduction abolished the restrained effect of circ_SNX27 absence on HCC cell development. Moreover, miR-637 curbed HCC cell malignant phenotype by regulating FGFR1.

CONCLUSION

Circ_SNX27 contributed to HCC development via miR-637/FGFR1 axis, offering a new idea for the treatment of HCC.

摘要

背景

环状 RNA(circRNAs)在癌症发展中充当关键的调控因子。然而,circRNA 分选连接蛋白 27(circ_SNX27)在肝细胞癌(HCC)中的潜在调控机制仍不清楚。

方法

采用实时定量聚合酶链反应和 Western blot 分析定量检测 circ_SNX27、微小 RNA-637(miR-637)和成纤维细胞生长因子受体 1(FGFR1)的水平。接下来,通过体外实验和体内移植瘤研究进行功能实验。通过双荧光素酶报告和 RNA 下拉实验揭示 miR-637 与 circ_SNX27 或 FGFR1 之间的关系。

结果

circ_SNX27 和 FGFR1 的水平上调,而 miR-637 的含量在 HCC 中降低。circ_SNX27 下调抑制 HCC 细胞的增殖、迁移和侵袭,并促进体外细胞凋亡,同时减弱体内肿瘤生长。circ_SNX27 作为 miR-637 的海绵体促进 FGFR1 的表达。miR-637 减少消除了 circ_SNX27 缺失对 HCC 细胞发育的抑制作用。此外,miR-637 通过调节 FGFR1 抑制 HCC 细胞的恶性表型。

结论

circ_SNX27 通过 miR-637/FGFR1 轴促进 HCC 发展,为 HCC 的治疗提供了新的思路。

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