2. Academic Validation
  3. HMMR mediates progression of nasopharyngeal carcinoma by inhibiting FAM83D ubiquitination and activating beta-catenin signaling pathway

HMMR mediates progression of nasopharyngeal carcinoma by inhibiting FAM83D ubiquitination and activating beta-catenin signaling pathway

  • Sci Rep. 2025 Oct 13;15(1):35701. doi: 10.1038/s41598-025-19641-z.
Fangyan Zhong # 1 2 3,  Tianzhu Lu # 1 2 3,  Ming Li # 1 2 4,  Dangchi Li # 5,  Anqi Yuan 2 3,  Hong Luo 2 3,  Jinglun Wang 6,  Lin Zhang 2 3,  Kai Huang 1 2,  Yong Su 2 3,  Junjun Chen 1 2,  Qing Dong 2 3,  Jing Wang 2 3,  Zhiliang Liu 2 7,  Chuansheng Huang 2 7,  Xiaochang Gong 1 2,  Xiaopeng Xiong 8 9,  Jingao Li 10 11 12
Affiliations

Affiliations

  • 1 Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 2 NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China.
  • 3 Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China.
  • 4 Department of Hepatobiliary Tumor Surgery, Department of Interventional Therapy, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China.
  • 5 Department of Ecology and Evolutionary Biology, University of California, Los Angeles, USA.
  • 6 Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, USA.
  • 7 Department of Pathology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China.
  • 8 NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China. xiongxiaopeng2021@foxmail.com.
  • 9 Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China. xiongxiaopeng2021@foxmail.com.
  • 10 Jiangxi Medical College, Nanchang University, Nanchang, China. lijingao@hotmail.com.
  • 11 NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China. lijingao@hotmail.com.
  • 12 Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China. lijingao@hotmail.com.
  • # Contributed equally.
PMID: 41083782 DOI: 10.1038/s41598-025-19641-z
Abstract

The hyaluronan-mediated motility receptor (HMMR) is widely expressed across various species and plays a crucial role in Cancer progression. However, its role in nasopharyngeal carcinoma (NPC) remains unexplored. Here, we identified a novel HMMR-FAM83D-β-catenin axis, which drives NPC progression through β-catenin signaling. Using bulk RNA Sequencing, single-cell RNA-sequencing, and immunohistochemistry, we determined that HMMR is highly expressed in NPC tissues, correlating with poor survival in NPC patients. In vitro assays demonstrated that modulating HMMR expression influenced NPC cell proliferation, migration, and invasion. In vivo, HMMR knockdown significantly inhibited tumor growth and metastasis in NPC models. HMMR was significantly upregulated in NPC tissues and correlated with worse patient survival. Mechanistically, HMMR was found to interact with the Wnt/β-catenin signaling pathway, affecting both pathway activation and β-catenin expression, as evidenced by RNA-seq and western blotting. Co-immunoprecipitation, mass spectrometry, and western blot analyses further revealed that HMMR interacts with Family with Sequence Similarity 83 Member D (FAM83D), stabilizing its expression by inhibiting its ubiquitination. This interaction, in turn, modulates β-catenin levels, driving NPC progression. Our findings reveal a novel HMMR-FAM83D-β-catenin axis that promotes NPC cell progression through Wnt/β-catenin signaling by modulating β-catenin signaling. HMMR could serve as a potential prognostic biomarker and therapeutic target for NPC, deepening our understanding of its role in disease progression.

Keywords

Family with sequence similarity 83 member d; Hyaluronan-mediated motility receptor; Nasopharyngeal carcinoma; Ubiquitination; Wnt/β-catenin signaling.

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