LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression

Abstract

Transforming growth factor-β (TGF-β) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-β regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. In cancer, TGF-β promotes cancer invasion and metastasis by enhancing the stemness and epithelial mesenchymal transition of cancer cells. However, TGF-β is highly pleiotropic in both tissue fibrosis and cancers, and thus, direct targeting of TGF-β may also block its protective anti-inflammatory and tumor-suppressive effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-β-driven tissue fibrosis and cancer progression with a high cell-type and disease specificity, serving as an ideal target for therapeutic development. In this review, the mechanism and translational potential of TGF-β-associated lncRNAs in tissue fibrosis and cancer will be discussed.

HOXA5-induced lncRNA DNM3OS promotes human embryo lung fibroblast fibrosis via recruiting EZH2 to epigenetically suppress TSC2 expression

“…Many studies interrogating the pathogenesis of IPF have found many diseases related to lncRNAs. LncRNA has been implicated in the regulation of transforming growth factor beta 1 (TGF-β1) ( 17 ). LncRNA Airn alleviate liver fibrosis via the Kruppel-like factor 2 (KLF2)-endothelial nitric oxide synthase (eNOS)-soluble guanylate cyclase (sGC) pathway ( 18 ), while Zinc finger E-box binding homeobox 1 antisense 1 ( ZEB1-AS1 ) contributes to lung fibrosis by facilitating EMT ( 19 ).…”

LncRNA HOTAIR down-expression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing TGF-β1 and ZEB1

“…It participates in cell proliferation and migration. It was also involved in epithelial-mesenchymal transformation (EMT) in normal tissue and tumors, and lncRNA HOTAIR has potential for cancer targeted therapy [ 3 , 4 ]. To predict and validate the target sites of lncRNA HOTAIR, first, to identify relevant targets and contact networks, we constructed an shRNA interference vector with low expression of lncRNA HOTAIR and transfected it into EOC SKOV3 cells.…”