2. Academic Validation
  3. NELFCD Promotes Colon Cancer Progression by Regulating the DUSP2-p38 Axis

NELFCD Promotes Colon Cancer Progression by Regulating the DUSP2-p38 Axis

  • Front Biosci (Landmark Ed). 2025 Apr 25;30(4):25221. doi: 10.31083/FBL25221.
Weiwei Dai 1,  Min Zhu 1,  Yujing Sun 2,  Baohong Xu 3,  Guorong Ma 4,  Haiyun Shi 1,  Peng Li 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, 100000, Beijing, China.
  • 2 Department of Laboratory, Peking University International Hospital, 100000, Beijing, China.
  • 3 Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, 100000, Beijing, China.
  • 4 Department of Pathology, Beijing Luhe Hospital Affiliated to Capital Medical University, 100000, Beijing, China.
PMID: 40302325 DOI: 10.31083/FBL25221
Abstract

Background: To investigate the significance of the negative elongation factor complex member C/D (NELFCD) in colon Cancer progression.

Methods: Immunohistochemistry staining, Western blot analysis, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to quantify the protein/gene levels. NELFCD-protein arginine methyltransferase 5 (PRMT5) interaction was determined by co-immunoprecipitation assay. A chromatin immunoprecipitation (ChIP) assay was performed to determine the interaction between the promoter region of dual specificity Phosphatase 2 (DUSP2), NELFCD, and PRMT5. Cell growth and cell cycle progression were assessed using the cell counting kit-8 proliferation assay, colony formation assay, and/or flow cytometry.

Results: NELFCD was upregulated in colon Cancer and promoted Cancer cell growth. In colon Cancer cells, the expression of NELFCD was negatively correlated with DUSP2 expression. The RNA Sequencing results indicated that genes in the mitogen-activated protein kinase (MAPK) signaling pathway as well as DUSP2 were affected by NELFCD. The ChIP Sequencing results revealed that DUSP2 and genes in the MAPK signaling pathway are direct targets of NELFCD. ChIP assay verified that PRMT5 is enriched at the promoter region of DUSP2 and that NELFCD overexpression promoted this enrichment. A co-immunoprecipitation assay demonstrated that NELFCD was bound to PRMT5, functioning as a macromolecular complex.

Conclusions: This study suggests that NELFCD promotes the progression of colon Cancer by recruiting PRMT5 to inhibit DUSP2 expression, which subsequently activates the p38 signaling pathway. Targeting the NELFCD-DUSP2-p38 signaling axis may be a promising therapeutic intervention for patients suffering from NELFCD-amplified tumors.

Keywords

DUSP2; NELFCD; PRMT5; colon cancer; p38.

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