The Interaction Between Long Non-Coding RNAs and Cancer-Associated Fibroblasts in Lung Cancer

Abstract

Despite great advances in research and treatment, lung cancer is still one of the most leading causes of cancer-related deaths worldwide. Evidence is mounting that dynamic communication network in the tumor microenvironment (TME) play an integral role in tumor initiation and development. Cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis, are the most important stroma component in the tumor microenvironment. Consequently, in-depth identification of relevant molecular mechanisms and biomarkers related to CAFs will increase understanding of tumor development process, which is of great significance for precise treatment of lung cancer. With the development of sequencing technologies such as microarray and next-generation sequencing, lncRNAs without protein-coding ability have been found to act as communicators between tumor cells and CAFs. LncRNAs participate in the activation of normal fibroblasts (NFs) to CAFs. Moreover, activated CAFs can influence the gene expression and secretion characteristics of cells through lncRNAs, enhancing the malignant biological process in tumor cells. In addition, lncRNA-loaded exosomes are considered to be another important form of crosstalk between tumor cells and CAFs. In this review, we focus on the interaction between tumor cells and CAFs mediated by lncRNAs in the lung cancer microenvironment, and discuss the analysis of biological function and molecular mechanism. Furthermore, it contributes to paving a novel direction for the clinical treatment of lung cancer.

Extracellular Vesicles Derived from Lung Cancer Cells Induce Transformation of Normal Fibroblasts into Lung Cancer-Associated Fibroblasts and Promote Metastasis of Lung Cancer by Delivering lncRNA HOTAIR

“…LncRNAs are critical players in the invasion and metastasis of LC [ 58 ]. In particular, lncRNAs carried by tumors participate in the activation of CAFs [ 21 , 32 ]. Importantly, lncRNA HOTAIR level is upregulated in LC [ 21 , 40 ].…”

“…In particular, lncRNAs carried by tumors participate in the activation of CAFs [ 21 , 32 ]. Importantly, lncRNA HOTAIR level is upregulated in LC [ 21 , 40 ]. Similarly, our findings revealed overexpressed HOTAIR levels in LC cells and their derived EVs, and HOTAIR was encapsulated in T-EVs.…”

“…Transforming growth factor- β (TGF- β ), fibroblast growth factor 2, epidermal growth factor, hypoxia, reactive oxygen species, and ncRNAs are the key regulators of fibroblast activation [ 36 , 37 ]. With the development of sequencing technologies such as gene chips and next generation sequencing, lncRNAs are identified to play a role as a transmitter between tumor cells and CAFs and participate in the activation of NFs to CAFs [ 21 ]. In addition, tumor cells and CAFs can communicate more directly through Exos-carrying lncRNAs, and Exos released by cancer cells can also promote the transformation and activation of CAFs [ 32 ].…”

“…LncRNA HOTAIR has been reported to be highly expressed in LC and promotes cisplatin resistance in non small-cell LC cells [ 21 , 40 ], thus being as a marker of abnormal regulation of the LC cell cycle [ 41 ]. Moreover, HOTAIR knockdown could partially reverse the promoting effect of Caveolin-1 on cell viability and invasiveness, and HOTAIR may be a new therapeutic target for LC [ 42 ].…”

The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer

“…Although the research on lncRNAs in the TME has just begun, important achievements in our understanding of the effects of lncRNAs on CAFs in the future are likely. Recently, with the rapid development of high-throughput sequencing technologies, lncRNAs have been found to be involved in communication between cancer cells and CAFs [ 94 ].…”