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Background: Many cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood., Methods: Association of SNP (rs140618127) in lncRNA LOC146880 with non-small cell lung cancer (NSCLC) was evaluated in a case-control study of 2707 individuals. The mechanism of the SNP's biologic influence was explored with in vitro and in vivo experiments, including plasmid transfection, siRNA knockdown, flow cytometry assessment, and assays of cell proliferation, migration, invasion, and colony formation., Results: Association analysis showed that A allele of SNP rs140618127 was associated with low risk of NSCLC in the Chinese population. Lab experiments indicated that SNP rs140618127 contained a binding site for miR-539-5p and the binding between miR-539-5p and LOC146880 resulted in declined phosphorylation of an oncogene, ENO1. The reduced phosphorylation of ENO1 led to decreased phosphorylation of PI3K and Akt, which is further linked to the decline in cell proliferation and tumor progression., Conclusion: The study demonstrates that SNP rs140618127 in lncRNA loc146880 provides an alternate binding site for microRNA miR-539-5p which affects the phosphorylation of ENO1 and activation of the PI3K and Akt pathway.

Background: It has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non-coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case-control study to address this issue., Methods: Using the TaqMan method, we genotyped 17 SNPs located in the 13 lncRNA genes in 1294 cases with NSCLC and 1729 healthy controls. Unconditional logistic regression and Cox proportional hazards regression were used to analyze the associations of these SNPs with NSCLC risk and patient survival, respectively. These analyses were also repeated in subgroups of cases and controls stratified by gender, age group, smoking status, disease stage, and histological type., Results: We identified three SNPs associated with NSCLC risk. For SNP rs498238, CC genotype was associated with lower risk compared to TT genotype (adjusted OR = 0.33, 95%CI: 0.11-0.97, P = 0.043). For rs16901995, CT/TT genotypes were associated with lower risk compared to CC genotype in non-smokers (adjusted OR = 0.78, 95%CI: 0.62-0.98, P = 0.035). Variant genotypes in rs219741 were associated with NSCLC risk in young patients, and the adjusted OR was 1.47 (95%CI: 1.03-2.10, P = 0.033) when compared to the wild genotype. No SNPs were found to be associated with patient overall survival in the study., Conclusion: The study suggests that some genetic polymorphisms in the lncRNA genes may influence the risk of NSCLC among Chinese., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Recently, long non‑coding RNAs (lncRNAs) have been shown to play critical roles in lung adenocarcinoma (LUAD). The present study aimed to explore the effect of LINC00982 and PRDM16 on clinical features and survival in LUAD. We found that LUAD patients demonstrated lower expression and copy number variation but higher methylation of long intergenic non‑protein coding RNA 982 (LINC00982) and PR domain containing 16 (PRDM16) compared with controls. Thus, we divided the LUAD patients into two groups according to the median expression of LINC00982 and PRDM16. Through differential expression, KEGG pathway enrichment and Ingenuity® Pathway Analysis (IPA), we found that patients with low expression of both LINC00982 and PRDM16 presented with more deregulated genes, as well as more significant pathways, than patients with high expression of these two genes. In addition, Kaplan‑Meier curves and Cox proportional hazards models revealed that patients with low expression of LINC00982, PRDM16 or both, showed poorer survival than the groups with high expression of LINC00982, PRDM16. We further used multivariate survival models to verify these results. Furthermore, we confirmed that the expression of LINC00982 and PRDM16 was significantly decreased in LUAD cell lines compared to normal cell lines in vitro. In conclusion, the present study revealed that LINC00982 and PRDM16 may serve as biomarkers or potential drug targets for the diagnosis and therapy of LUAD.

Background/aims: Ecological studies have shown that air pollution and prevalence of cigarette smoking are positively correlated. Evidence also suggests a synergistic effect of cigarette smoking and PM2.5 exposure (Environmental Particulate Matter ≤ 2.5 µm in diameter) on lung cancer risk. We aimed to evaluate the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality and determine its underlying mechanisms in vitro., Methods: "MOVER" method was used to analyze the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality. Cell autophagy and malignant behaviors induced by cigarette smoke extract (CSE) and PM2.5 exposure were examined in vitro. Gene expression was examined by qRT-PCR and western blot. RNA and protein interaction was determined using a RNA binding protein immunoprecipitation assay., Results: An increased risk for lung cancer death (RERI (the relative excess risk) =0.28) was observed with a synergistic interaction between cigarette smoking and PM2.5 pollution. Cell migration, invasion, EMT (epithelial-mesenchymal transition) and autophagy were elevated when lung cancer cells were treated with CSE and PM2.5 in combination. A lncRNA, named lung cancer progression-association transcript 1 (LCPAT1), was up-regulated after the treatment of CSE and PM2.5, and knocking down the lncRNA impaired the effect of CSE and PM2.5 on lung cancer cells. In addition, LCPAT1 was shown to bind to RCC2, and RCC2 mediated the effect of LCPAT1 on cell autophagy, migration, invasion and EMT in lung cancer., Conclusions: Our results suggest that combined exposure to CSE and PM2.5 induces LCPAT1 expression, which up-regulates autophagy, and promotes lung cancer progression via RCC2., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objective: To determine if lncRNA expression can be used for the prognoses of patients diagnosed with lung adenocarcinoma (LUAD) patients., Methods: The Cancer Genome Atlas database was used to identify 409 LUAD patients for whom there were both, gene expression data and relevant clinical information available. LncRNAs were then selected from the expression data through record linkage between the National Center for Biotechnology Information (NCBI) and Ensemble databases. lncRNAs with significantly different expression levels between normal and tumor tissues were screened, and those whose levels correlated with a positive LUAD prognosis were identified. Based on the expression of the selected lncRNAs, an unsupervised learning method was used to cluster these patients into two groups, and survival analyses were performed to assess the overall survival (OS) between the two groups. Receiver operating characteristic curves were used to calculate the specificity and sensitivity of the models based on the presence of these lncRNAs, and the model was tested with another dataset from the Gene Expression Omnibus., Results: A total of 151 lncRNAs were found to be differentially expressed between tumor and normal tissues (permutation p-values <0.05) based on the Cancer Genome Atlas dataset, and 20 lncRNAs were associated with OS. Two lncRNAs (DKFZP434 L187 and LOC285548) were correlated with LUAD. All patients with high expression of these two lncRNAs from the two datasets exhibited poor OS compared with those with low expression (p < 0.05)., Conclusions: The expression of DKFZP434 L187 and LOC285548 may have prognostic value for the OS of LUAD patients.

Background: Evidence shows that individuals who are under long-term exposure to environmental PM 2.5 are at increased risk of lung cancer. Various laboratory experiments also suggest several mechanistic links between PM 2.5 exposure and lung carcinogenesis. However, a long non-coding RNA (lncRNA) mediated pathogenic change after PM 2.5 exposure and its potential roles in tumorigenesis and disease progression have not been reported., Methods: Cytotoxicity induced by PM 2.5 was assessed by using scanning electron microscopy and transmission electron microscopy. ROS generation, autophagy, and metastasis induced by PM 2.5 were detected by using comprehensive approaches. Expression of lncRNA-loc146880 and lc3b (autophagy marker) in A549 cells, lung tissue and serum were determined by RT-PCR and Western blotting., Results: PM 2.5 could be internalized into lung cancer cells, resulting in marked increases in ROS levels and autophagy. ROS may be responsible for increased expression of loc146880 which further up-regulates autophagy. Both loc146880 and autophagy could promote lung tumor cell migration, invasion and EMT. In addition, a positive correlation was observed between loc146880 expression and lc3b levels in tumor tissues and serum of lung cancer patients., Conclusion: Taken together, our data suggest that PM 2.5 exposure induces ROS, which activates loc146880 expression. The lncRNA, in turn, up-regulates autophagy and promotes the malignant behaviors of lung cancer cells., General Significance: The results show the toxicological effects of PM 2.5 in lung tumor progression and metastasis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

To identify what long non-coding RNAs (lncRNAs) are involved in non-small cell lung cancer (NSCLC), we analyzed microarray data on gene expression and methylation. Gene expression chip and HumanMethylation450BeadChip were used to interrogate genome-wide expression and methylation in tumor samples. Differential expression and methylation were analyzed through comparing tumors with adjacent non-tumor tissues. LncRNAs expressed differentially and correlated with coding genes and DNA methylation were validated in additional tumor samples using RT-qPCR and pyrosequencing. In vitro experiments were performed to evaluate lncRNA's effects on tumor cells. We identified 8,500 lncRNAs expressed differentially between tumor and non-tumor tissues, of which 1,504 were correlated with mRNA expression. Two of the lncRNAs, LOC146880 and ENST00000439577, were positively correlated with expression of two cancer-related genes, KPNA2 and RCC2, respectively. High expression of LOC146880 and ENST00000439577 were also associated with poor survival. Analysis of lncRNA expression in relation to DNA methylation showed that LOC146880 expression was down-regulated by DNA methylation in its promoter. Lowering the expression of LOC146880 or ENST00000439577 in tumor cells could inhibit cell proliferation, invasion and migration. Analysis of microarray data on gene expression and methylation allows us to identify two lncRNAs, LOC146880 and ENST00000439577, which may promote the progression of NSCLC.