ABSTRACT
OBJECTIVE To explore the dyna mic change of lncRNA expression during lung carcino-genesis induced by urethane.METHODS A total of 40 BALB/c mice received weekly ip injection of urethane 1 g·kg -1 for four continuous weeks,mice were euthanized at 12th week or 24th week after the first urethane treat ment,respectively.The RNA of lung tissues were isolated and used for microarray analysis.Based on the results of the microarray we selected lncRNA-AK017233 for additional qPCR analysis in individual mouse.RESULTS The incidence of lung cancer were 85% and 100% at 12th week and 24th week after the first ad ministration of urethane,respectively.The multiplicity and dia meter of lung tu mors in 24 weeks treated group were statistically significant fro m those in 12 weeks treated group (P<0.01 ),and pathological analysis showed that tu mors were classifiable as moderately differ-entiated adenocarcino ma.Total of 26 Down-regulated lncRNAs in which lncRNA-AK017233 stand for the most down-regulated lncRNA were identified by microcarray analysis.qPCR detected that the lncRNA-AK017233 was significantly altered by 0.33 ti mes in lung tu mors of urethane treated group at 12th week, co mpared to parallel lung tissues in urethane treated group at 12th week.AK017233 expression of ure-thane treated group was significantly reduced by 0.22 ti mes at 24th week,co mpared to parallel lung tis-sues in urethane treated group at 24th week.CONCLUSION LncRNA-AK017233 was consistently down-regulated during urethane induced lung carcinogenesis.
ABSTRACT
<p><b>OBJECTIVE</b>To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK)-induced early stage lung carcinogenesis.</p><p><b>METHODS</b>A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.</p><p><b>RESULTS</b>No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.</p><p><b>CONCLUSION</b>The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.</p>
Subject(s)
Animals , Humans , Male , Rats , Adenocarcinoma , Carcinogenesis , Cell Line, Tumor , Gene Expression Regulation , Physiology , Lung , Pathology , Lung Neoplasms , Blood , Metabolism , MicroRNAs , Blood , Genetics , Metabolism , Nitrosamines , Pharmacology , Rats, Inbred F344ABSTRACT
PURPOSE: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma. METHODS: Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis. RESULTS: During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index. CONCLUSIONS: These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.