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.
Highlights
JIANG et al: ROLES OF long non‐coding RNAs (lncRNAs) IN LUNG CANCER physiological and pathological functions [11]
These findings suggest that Smoke‐associated and cancer‐associated lncRNA‐1 (SCAL1) has an important role in the antioxidant pathway [23]
Regulates miR‐124/signal transducer and activator of transcription 3 (STAT3), miR‐206/Akt and miR‐204/SLUG; increases splicing factor (SR) phosphorylation; suppress P53 activity; enhances specificity protein 1 (SP1) and C‐X‐C motif chemokine ligand 5 (CXCL5) expression; downregulates MIA SH3 domain ER export factor 2 (MIA2) and ROBO1 and upregulates glypican 6 (GPC6), LPHN2 and AT binding cassette subfamily A member 1 (ABCA1); releases PTB‐associated splicing factor (PSF) from G antigen 6 (GAGE6); Sponges miR‐101 to regulate SRY‐box transcription factor 9 (SOX9) and MCL1; activates STAT3 signaling and upregulates multidrug resistance‐associated protein 1 (MRP1) and multidrug resistance 1 (MDR1) Inhibits p53; regulates miR‐326/Phox2, homeobox A5 (HOXA5) and miR‐613 expression; enhances 14‐3‐3σ expression; interacts with LSH to regulate FOXA2/FOXA1 expression ratio; Decreases p21 and activates Wnt signaling; decreases DNMT1 and DNMT3b resulting in upregulation of HOXA1; activates transforming growth factor (TGF)‐α/EGFR and inhibits Bax/caspase‐3; increases phosphorylation of ULK1 and enhances autophagy; downregulates Wnt inhibitory factor 1 (WIF‐1) and activates Wnt signaling Regulates miR‐17/STAT3, miR‐484/Rho associated coiled‐coil containing protein kinase 2 (ROCK2) and miR‐196b/LIN28B; interacts and attenuates SAHH; increases BPDE‐DNA adduct formation; Regulates miR‐200a/miR‐200b/matrix metalloproteinase 9 (MMP9); Decreases miR‐195 expression Inhibits P15, P21 and Krüppel‐like factor 2 (KLF2) expression
Summary
Many large‐scale investigations, including microarray profiling and deep sequencing data, have revealed that the derangement of lncRNA expression is a primary feature in lung cancer initiation and progression [18,19]. Various transcription factors can bind within the promoter regions of lncRNAs to activate or inhibit their transcription. Treatment with the methyl donor, S‐adenosylmethionine, suppresses MALAT1 expression in lung cancer cells [26] In such cases, the lncRNA sprouty RTK signaling antagonist 4 intronic transcript 1 (SPRY4‐IT1), located at chromosome 5q31.3, is upregulated and promotes proliferation and metastasis of cancer cells [27]. HOTAIR enhances H3K27me modification within the p53 promoter and inhibits p53 expression in the lung cancer cell line A549. Octamer binding transcription factor 4 (OCT4) has been reported to increase MALAT1 transcription by binding to its promoter enhancer region, thereby inducing upregulation of MALAT1 expression in lung cancer [38]. MALAT1 expression has been shown to be regulated by TAR DNA‐binding protein 43 (TDP43) in lung cancer [39]
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