Zinc finger protein 383 suppresses tumor growth in NSCLC by upregulating DUSP16 expression to inactivate ERK signaling
- Tissue Cell. 2026 Oct:102:103640. doi: 10.1016/j.tice.2026.103640.
- 1. Department of Pathology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Pathology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China. Electronic address: [email protected].
- 2. Department of Pathology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Pathology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
- 3. Department of Pathology, Fuzhou Second General Hospital, Fuzhou 350212, China.
Purpose: Despite its known function as a KRAB-domain Zinc Finger Protein and MAPK pathway suppressor, the specific role of Zinc Finger Protein 383 (ZNF383) in non-small cell lung Cancer (NSCLC) remains elusive. To address this, we assessed ZNF383 expression in NSCLC and examined its effects on tumor cell proliferation.
Methods: We performed RT-qPCR, western blotting, and immunohistochemistry to detect ZNF383 expression in NSCLC cells and tissues. Survival outcomes were assessed by the Kaplan-Meier method. The functional role of ZNF383 was elucidated through a series of in vitro and in vivo experiments. To investigate its transcriptional regulatory mechanism, we conducted dual-luciferase reporter assays and confirmed specific promoter binding via ChIP-qPCR.
Results: Low ZNF383 expression in NSCLC patients was linked to aggressive clinicopathology (poor differentiation, advanced stage, metastasis) and poor survival. ZNF383 acted as a tumor suppressor: its overexpression inhibited cell proliferation, colony formation, cell cycle progression, and tumor growth, whereas its knockdown promoted these processes. Mechanistically, ZNF383 (via its KRAB domain) upregulate DUSP16, leading to ERK inactivation, p27 accumulation, and G1 arrest.
Conclusion: ZNF383 upregulate DUSP16 expression, consequently inactivating ERK signaling to inhibit NSCLC progression. Targeting the ZNF383/DUSP16/ERK axis presents a novel strategy for NSCLC therapy.