Bingyan Xu, Meihua Chen*
Departments of Hematology and Geriatrics, The Second People’s Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213000 Jiangsu, China.
- Corresponding Author: Meihua Chen; E-mail: meihua_chen2028@163.com
Abstract
Background
Hodgkin lymphoma (HL) is a malignant tumour of the lymphoid system with complex pathogenesis. Increasing evidence suggests that long non-coding RNAs (lncRNAs) participate in HL progression, yet the role of poly(C)-binding protein 1 antisense RNA 1 (PCBP1-AS1) remains unclear.
Methods
Human HL cell lines (KM-H2, L1236, L428 and L540) and germinal-centre B cells were analysed for PCBP1-AS1, miR-516b-5p and TRIM2 expression by RT-qPCR and western blotting. Loss- and gain-of-function assays, including CCK-8, colony-formation and Transwell assays, were used to assess cell proliferation, migration and invasion. RNA pull-down, luciferase reporter and RNA immunoprecipitation assays verified molecular interactions among PCBP1-AS1, miR-516b-5p and TRIM2.
Results
PCBP1-AS1 was markedly up-regulated in HL cells compared with germinal-centre B cells. Silencing PCBP1-AS1 significantly reduced HL-cell proliferation, colony formation, migration and invasion. Mechanistically, PCBP1-AS1 directly bound to miR-516b-5p, which was down-regulated in HL cells, thereby relieving the inhibitory effect of miR-516b-5p on its downstream target TRIM2. Inhibition of miR-516b-5p reversed the suppressive effects of PCBP1-AS1 knockdown, while TRIM2 overexpression abolished the inhibitory effects of miR-516b-5p up-regulation on HL-cell malignant phenotypes.
Conclusion
PCBP1-AS1 promotes HL progression by acting as a competing endogenous RNA that sponges miR-516b-5p to up-regulate TRIM2. The PCBP1-AS1/miR-516b-5p/TRIM2 axis may represent a promising molecular target for HL therapy.
Keywords: Hodgkin lymphoma, PCBP1-AS1, miR-516b-5p, TRIM2