Author:
Zhuang Yan,Wang Xiang,Nguyen Hong T,Zhuo Ying,Cui Xinpeng,Fewell Claire,Flemington Erik K,Shan Bin
Abstract
Abstract
Background
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. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms.
Findings
We 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.
Conclusions
Our 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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Biology,Hematology
Cited by
104 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献