Abstract
BackgroundThe tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms.FindingsWe investigated whether the expression of lincRNAs was regulated by the tumor promoting Col-1. In a three-dimensional organotypic culture model using the reconstituted basement membrane ECM Matrigel (rBM 3-D), supplementation of Col-1 disrupted acini, a differentiation feature of well-differentiated lung adenocarcinoma cells, and concurrently induced the expression of a tumor-promoting lincRNA, HOX transcript antisense RNA (HOTAIR). Induction of HOTAIR by Col-1 was diminished by a neutralizing antibody against the Col-1 receptor α2β1 integrin. Col-1 activates the expression of a reporter gene controlled by the human HOTAIR promoter. Moreover the expression of HOTAIR and Col-1 was concurrently up-regulated in human non-small cell lung cancer.ConclusionsOur findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. These initial results warrant further investigation of HOTAIR and other lincRNA genes in lung tumorigenesis.
Highlights
The tumor microenvironment is a crucial determinant in tumor progression
Our findings indicate that tumor-promoting Type I collagen (Col-1) up-regulates the expression of HOX transcript antisense RNA (HOTAIR) in non-small cell lung cancer (NSCLC) cells
The tumor microenvironment is aberrantly enriched with interstitial extracellular matrix (ECM), such as type I collagen (Col-1) [1]
Summary
The tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Conclusions: Our findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. Col-1 disrupts acinar morphogenesis of lung and mammary epithelial cells in rBM 3-D culture and promotes tumor progression in vivo [5,6].
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