Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling

• Published in: iScience Vol. 26; no. 11; p. 108201
• Main Authors: Xia, Lingyun, Zhang, Tianshu, Yao, Juncheng, Lu, Kaitian, Hu, Ziqiu, Gu, Xinsheng, Chen, Yongji, Qin, Shanshan, Leng, Weidong
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 17.11.2023; Elsevier
• Subjects: Cancer; Cell biology; Cell biology; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108201

Accumulating evidence has shown that fibromodulin (FMOD) plays a pivotal role in tumorigenesis and metastasis. However, the biological function of FMOD in oral squamous cell carcinoma (OSCC) remains largely unclear to date. In this study, we confirmed that FMOD was overexpressed and showed a significant association with malignant progression and lymph node metastasis in OSCC. Depletion of FMOD inhibited OSCC proliferation and metastasis in vitro and in vivo. RNA sequencing, western blotting, and rescue assays verified that FMOD exerted oncogenic roles in OSCC via activation of EGFR signaling. In addition, FMOD was proved to be a putative target gene of miR-338-3p. Taken together, FMOD overexpression due to the reduced level of miR-338-3p promotes OSCC by activating EGFR signaling. Our findings provide direct evidence that targeting FMOD could be a promising therapeutic strategy for OSCC patients. [Display omitted] •FMOD mRNA and protein are upregulated in OSCC•FMOD overexpression is closely correlated with OSCC progression and metastasis•FMOD depletion inhibits OSCC by blocking EGFR signaling•FMOD mRNA is directly targeted by miR-338-3p Cell biology; Cancer