The landscape of long non-coding RNAs in tumor stroma

Long non-coding RNAs (lncRNAs) are associated with cancer development, while their relationship with the cancer-associated stromal components remains poorly understood. In this review, we performed a broad description of the functional landscape of stroma-associated lncRNAs in various cancers and their roles in regulating the tumor-stroma crosstalk. We carried out a systematic literature review of PubMed, Scopus, Medline, Bentham, and EMBASE (Elsevier) databases by using the keywords “LncRNAs in cancer,” “LncRNAs in tumor stroma,” “stroma,” “cancer-associated stroma,” “stroma in the tumor microenvironment,” “tumor-stroma crosstalk,” “drug resistance of stroma,” and “stroma in immunosuppression” till July 2020. We collected the latest articles addressing the biological functions of stroma-associated lncRNAs in cancer. These articles reported that dysregulated stroma-associated lncRNAs play significant roles in modulating the tumor microenvironment (TME) by the regulation of tumor-stroma crosstalk, epithelial to mesenchymal transition (EMT), endothelial to mesenchymal transition (EndMT), extracellular matrix (ECM) turnover, and tumor immunity. The tumor stroma is a substantial portion of the TME, and the dysregulation of tumor stroma-associated lncRNAs significantly contributes to cancer initiation, progression, angiogenesis, immune evasion, metastasis, and drug resistance. Thus, stroma-associated lncRNAs could be potentially useful targets for cancer therapy. [Display omitted] •Tumor surrounding stromal long non-coding RNAs (lncRNAs) are associated with cancer initiation, growth, aggressiveness, progression, angiogenesis, metastasis, and drug resistance•Stromal dysregulated lncRNAs play important physiological functions for modulating the tumor microenvironment (TME)•Stromal dysregulated lncRNAs are associated with tumor-stroma crosstalk and tumor immunity, epithelial to mesenchymal transition (EMT), endothelial to mesenchymal transition (EndMT), extracellularmatrix (ECM) turnover, tumor immunity