1. Academic Validation
  2. LncRNA NEAT1_1 suppresses tumor-like biologic behaviors of fibroblast-like synoviocytes by targeting the miR-221-3p/uPAR axis in rheumatoid arthritis

LncRNA NEAT1_1 suppresses tumor-like biologic behaviors of fibroblast-like synoviocytes by targeting the miR-221-3p/uPAR axis in rheumatoid arthritis

  • J Leukoc Biol. 2022 Mar;111(3):641-653. doi: 10.1002/JLB.3A0121-067RRR.
Manli Wang 1 Yixiong Chen 1 Xuan Bi 1 Xiqing Luo 1 Zuoyu Hu 1 Yan Liu 1 Xiaoyi Shi 1 Weizhen Weng 1 Biyao Mo 2 Yan Lu 3 Yunfeng Pan 1
Affiliations

Affiliations

  • 1 Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 2 Division of Rheumatology, Department of Internal Medicine, Hainan General Hospital, Hainan affiliated Hospital of Hainan Medical University, Haikou, China.
  • 3 Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Abstract

Fibroblast-like synoviocytes (FLSs) are the predominant effector cells in the pathological progression of rheumatoid arthritis (RA). Therefore, elucidating the underlying molecular mechanism of the biologic behaviors in RA-FLSs will be helpful in developing the potent targets for the treatment of RA. We have previously documented that the tumor-like biologic behaviors of RA-FLSs are exacerbated by urokinase-type plasminogen activator receptor (uPAR), a specifically up-regulated receptor in RA-FLSs. Here, we investigate the further mechanism of uPAR and clarify its function in RA-FLSs. We demonstrate that miR-221-3p positively correlates to uPAR and regulates uPAR level in RA-FLSs. Simultaneously, one long noncoding RNA, nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) is identified, which can predictively target miR-221-3p at three sites, indicating a strong possibility of being a competing endogenous RNA in RA-FLSs. Interestingly, NEAT1_1 and miR-221-3p can colocate in the nucleus and cytoplasm in RA-FLSs. Importantly, NEAT1_1 can act as a rheostat for the miR-221-3p/uPAR axis and the downstream JAK signaling. In line with the biologic function, NEAT1_1 negatively regulates the tumor-like characters, and cytokine secretions of RA-FLSs. Collectively, our data provide new insight into the mechanisms of NEAT1_1 in modulating RA-FLSs tumor-like behaviors. The targeting of NEAT1_1 and miR-221-3p/uPAR axis may have a promising therapeutic role in patients with RA.

Keywords

NEAT1_1; fibroblast-like synoviocytes; miR-221-3p; rheumatoid arthritis.

Figures
Products
Inhibitors & Agonists
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-B0496
    99.91%, Cathepsin抑制剂
Other Products