Cancer-associated fibroblasts promote tumor progression by lncRNA-mediated RUNX2/GDF10 signaling in oral squamous cell carcinoma

Mol Oncol. 2022 Feb;16(3):780-794. doi: 10.1002/1878-0261.12935. Epub 2021 Jun 10.

Abstract

Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in tumor and exert a pro-tumoral effect in cancer progression. Numerous evidence shows long non-coding RNA (lncRNA) abnormally regulates gene expression in various cancers. However, little is known about the role of lncRNA in the interaction between CAF and cancer cells. Here, we first identify an uncharacterized lncRNA, LOC100506114, which is significantly upregulated in CAF and is involved in the functional transformation of normal fibroblasts (NF) and CAF. Expression of LOC100506114 enhances the expression of fibroblast activation protein alpha and α-smooth muscle actin in NF and promotes malignant characteristics of NF and CAF in vivo and in vitro. The profile of gene co-expression analysis shows that growth differentiation factor 10 (GDF10) is positively correlated with the expression of LOC100506114. CAF promote stromal fibroblast activation and the proliferation and migration of tumor cells by secreting GDF10. Our data demonstrate that lncRNA plays a critical role in the interplay of stromal fibroblasts and tumor cells in oral squamous cell carcinoma.

Keywords: cancer-associated fibroblasts; lncRNA; transformation; tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer-Associated Fibroblasts* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Fibroblasts / metabolism
  • Growth Differentiation Factor 10 / metabolism
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Mouth Neoplasms* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Core Binding Factor Alpha 1 Subunit
  • GDF10 protein, human
  • Growth Differentiation Factor 10
  • RNA, Long Noncoding
  • RUNX2 protein, human