WISP-1 Promotes Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells via the miR-153-3p/Snail Axis

Abstract

Around half of all patients with oral squamous cell carcinoma (OSCC) present with lymphatic metastasis, a strong predictor of poor survival. Improving survival rates depends on preventing the first step in the “invasion-metastasis cascade,” epithelial-to-mesenchymal transition (EMT), and developing antilymphangiogenesis therapies that antagonize lymphatic metastasis. The extracellular matrix-related protein WISP-1 (WNT1-inducible signaling pathway protein-1) stimulates bone remodeling and tumor progression. We have previously reported that WISP-1 promotes OSCC cell migration and lymphangiogenesis induced by vascular endothelial growth factor C (VEGF-C). This investigation sought to determine the role of WISP-1 in regulating EMT in OSCC. Our analysis of oral cancer data from The Cancer Genome Atlas (TCGA) database revealed significant and positive associations between levels of WISP-1 expression and clinical disease stage, as well as regional lymph node metastasis. We also found higher levels of WISP-1 expression in serum samples obtained from patients with OSCC compared with samples from healthy controls. In a series of in vitro investigations, WISP-1 activated EMT signaling via the FAK/ILK/Akt and Snail signaling transduction pathways and downregulated miR-153-3p expression in OSCC cells. Our findings detail how WISP-1 promotes EMT via the miR-153-3p/Snail axis in OSCC cells.

M6A-related bioinformatics analysis reveals that HNRNPC facilitates progression of OSCC via EMT

“…In addition, HNRNPC also promoted cell proliferation and inhibited apoptosis by bounding to primary miR-21 (pri-miR-21) directly and promoted miR-21 expression in glioblastoma [22]. Increasing number of studies demonstrated that EMT was markedly relevant to OSCC progression [23][24][25]. In our study, expression of N-cadherin, MMP9, Vimentin were up-regulated and E-cadherin was down-regulated after overexpression of HNRNPC.…”

Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification

“…Our findings are just one example of how the matricellular protein WISP1 alters cellular fate and differentiation decisions. Past studies have implicated WISP1 in the balance of osteoblast versus adipocyte formation (38,39) and, more broadly, epithelial cells adopting a mesenchymal cell fate (epithelial-mesenchymal transition) (40)(41)(42)(43). As CCN family members, including WISP1, have numerous extracellular binding partners it is understandable that they may have context-dependent effects on cellular differentiation.…”

A Novel RNA-Seq-Based Model for Preoperative Prediction of Lymph Node Metastasis in Oral Squamous Cell Carcinoma

“…As per previous studies, CCBE1 is indispensable for the development of lymphatic vessels which have important roles in lymphangiogenesis and cancer metastasis [ 30 ]. Tumor lymphangiogenesis plays an important role in LNM of OSCC [ 31 – 33 ]. Hogan et al suggested that CCBE1 may be an extracellular guidance molecule and an independent factor for normal lymphoblasts to germinate or even migrate [ 34 ].…”