NFIC1 通过干扰素介导的 Jak-STAT 通路抑制乳腺癌细胞的迁移和侵袭。

NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway.

机构信息

China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, 130033, China; School of Life Sciences, Jilin University, Changchun, Jilin, 130012, China.

China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, 130033, China.

出版信息

Arch Biochem Biophys. 2022 Sep 30;727:109346. doi: 10.1016/j.abb.2022.109346. Epub 2022 Jul 5.

DOI:10.1016/j.abb.2022.109346

PMID:35798053

Abstract

NFIC1, the longest isoform of NFIC, is essential for the regulation on spatiotemporal expression of drug-metabolizing genes in liver. However, the role of NFIC1 in breast cancer is not clear. Here we showed that increased expression of NFIC1 suppressed the migration and invasion of MCF-7 cells. NFIC1 overexpression increased the expression of IFNB1, IFNL1, IFNL2 and IFNL3, and the activation of interferon-mediated Jak-STAT pathway was enhanced by NFIC1 overexpression. Treatment with Jak-STAT pathway inhibitors, Filgotinib or Ruxolitinib, reversed the suppressive effects of NFIC1 overexpression on migration and invasion of MCF-7 cells. In addition, we found that MX1 and MX2, two target genes of Jak-STAT pathway, mediated the migration and invasion of MCF-7 cells. These results demonstrated that NFIC1 inhibited the migration and invasion in MCF-7 cells through interferon-mediated activation of Jak-STAT pathway, indicating that Jak-STAT pathway might be a potential therapeutic target for preventing breast cancer metastasis.

摘要

NFIC1 是 NFIC 的最长异构体，对肝脏中药物代谢基因的时空表达调控至关重要。然而，NFIC1 在乳腺癌中的作用尚不清楚。本研究表明，NFIC1 表达增加抑制 MCF-7 细胞的迁移和侵袭。NFIC1 过表达增加 IFNB1、IFNL1、IFNL2 和 IFNL3 的表达，NFIC1 过表达增强干扰素介导的 Jak-STAT 通路的激活。Jak-STAT 通路抑制剂 Filgotinib 或 Ruxolitinib 处理可逆转 NFIC1 过表达对 MCF-7 细胞迁移和侵袭的抑制作用。此外，我们发现 Jak-STAT 通路的两个靶基因 MX1 和 MX2 介导 MCF-7 细胞的迁移和侵袭。这些结果表明，NFIC1 通过干扰素介导的 Jak-STAT 通路激活抑制 MCF-7 细胞的迁移和侵袭，表明 Jak-STAT 通路可能是预防乳腺癌转移的潜在治疗靶点。