Long non‑coding RNAs in lung cancer: Regulation patterns, biologic function and diagnosis implications (Review)

Abstract

Lung cancer is the most common malignancy with the highest mortality worldwide. Emerging research has demonstrated that long non‑coding RNAs (lncRNAs), a key genomic product, are commonly dysregulated in lung cancer and have significant functions in lung cancer initiation, progression and therapeutic response. lncRNAs may interact with DNA, RNA or proteins, as tumor suppressor genes or oncogenes, to regulate gene expression and cell signaling pathways. In the present review, first a summary was presented of the causal effects of dysregulated lncRNAs in lung cancer. Next, the function and specific mechanisms of lncRNA‑mediated tumorigenesis, metastasis and drug resistance in lung cancer were discussed. Finally, the potential roles of lncRNAs as biomarkers for lung cancer were explored.

Figure 1

Schematic plot of regulation patterns of dysregulated lncRNAs in lung cancer. (A) Chemical compounds and hypoxia affect lncRNA expression to promote cancer progression. (B) Changes in epigenetic modification of lncRNAs can regulate the development of lung cancer. (C) Various transcription factors can interact with lncRNAs to activate or inhibit their transcription, subsequently affecting cancer progression. lncRNA, long non-coding RNA.

Figure 2

Roles of lncRNA-mediated regulatory pathways in proliferation of lung cancer cells. According to their functions, lncRNAs were classified into two categories: Oncogenic lncRNAs (orange) are upregulated in lung cancer, enhancing growth and proliferation of lung cancer cells; whereas tumor suppressor lncRNAs (purple) are downregulated in lung cancer, inhibiting proliferation. lncRNA, long non-coding RNA.

Figure 3

Roles of lncRNA-mediated regulatory pathways in invasion and metastasis of lung cancer. lncRNAs act as sponges for miRNAs or regulate their downstream target genes, thereby promoting invasion and metastasis of lung cancer cells. lncRNA, long non-coding RNA; miRNA, microRNA.

Figure 4

lncRNAs mediate drug and radiation resistance. Tumor suppressor lncRNAs can regulate EGFR, IGF-1R, the Wnt signaling pathway and p53 to inhibit resistance of cancer cells towards drug and radiation therapy. Oncogenic lncRNAs promote resistance via multiple pathways, target genes and miRNAs. lncRNA, long non-coding RNA; EGFR, epidermal growth factor receptor; IGF-1R, insulin-like growth factor 1 receptor; miRNA, microRNA.