LncRNA RP11-116G8.5 promotes the progression of lung squamous cell carcinoma through sponging miR-3150b-3p/miR-6870-5p to upregulate PHF12/FOXP4.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is one of the commonest malignancies worldwide. Long noncoding RNAs (lncRNAs) have been revealed to engage in cancer development. LncRNA RP11-116G8.5 is a new founded lncRNA that has not been clearly elucidated in LUSC. MATERIALS AND METHODS: Expression levels of RNAs in LUSC cells were measured through qRT-PCR. To identify the functions of RP11-116G8.5, CCK-8 assay, colony formation assay and EdU assay were conducted in indicated LUSC cells. Mechanism experiments, including RNA pull down assay, Ago2-RIP assay and luciferase reporter assay were performed to demonstrate the interaction between RP11-116G8.5 and miR-3150b-3p/miR-6870-5p. Meanwhile, the interaction between miR-3150b-3p/miR-6870-5p and their downstream targets PHD finger protein 12 (PHF12), and forkhead box P4 (FOXP4) were also proven in the same methods. RESULTS: RP11-116G8.5 was expressed at high level in LUSC cell lines. Down-regulated RP11-116G8.5 repressed cell proliferation, migration and invasion, but accelerated apoptosis. Furthermore, it was proven that RP11-116G8.5 could act as sponges for miR-3150b-3p and miR-6870-5p these miRNAs were found to act as cancer suppressors in LUSC cells. PHF12 and FOXP4 were verified as the target gene of miR-3150b-3p and miR-6870-5p separately. Overexpression of PHF12 and FOXP4 could reverse the repressive effect of RP11-116G8.5 knockdown on LUSC progression. Additionally, Paired Box 5 (PAX-5) was proven to be the transcription factor for RP11-116G8.5 in LUSC cells. CONCLUSIONS: LncRNA RP11-116G8.5 promotes malignant behaviors of LUSC through sponging miR-3150b-3p/miR-6870-5p to upregulate PHF12/FOXP4 expression. AVAILABILITY OF DATA: The research data is confidential.

Application Value of Broadband 3-Dimensional Impulse Oscillometry in COPD.

OBJECTIVE: To explore the correlation of respiratory resistance in stable COPD patients measured by broadband 3-dimensional impulse oscillometry (3D-IOS) and traditional pulmonary function test (PFT). To access the diagnostic value of 3D-IOS in COPD. METHODS: A total of 107 COPD patients and 61 healthy subjects as controls were chosen to collect and statistically analyze the data of R5, R5-R20, R20, X5 and Fres measured by broadband 3D-IOS and FEV1%pred, FVC%pred and FEV1/FVC by PFTs. The diagnostic value of broadband 3D-IOS parameters in COPD was evaluated by receiver operating characteristic curve (ROC). 3D-colored images used to show dynamic changes of respiratory resistance in COPD. RESULTS: The COPD group showed significant increases in R5, R20, R5-R20 and Fres, and a decrease in X5 (P<0.05). With the increase of GOLD grade, R5, R5-R20 and Fres increased whereas X5 decreased (P<0.05). Compared with FEV1%pred, FVC%pred and FEV1/FVC in the COPD group, R5, R5-R20 and Fres were negatively collated (P<0.05), whereas X5 was positively collated (P<0.01). R20 was uncorrelated with the traditional lung function parameters (P>0.05). Fres and FEV1/FVC (r=-0.467), and X5 and FEV1%pred (r=0.412) showed the strongest correlation. The AUC of R5, R5-R20, X5 and Fres was 0.7808, 0.7659, 0.8947 and 0.9095, respectively. Typical 3D-colored images of COPD displayed a green pattern in the inhalation phase and yellow-red-blue graduation in the expiration phase. CONCLUSION: R5, R5-R20, X5 and Fres measured by broadband 3D-IOS can reflect the change of respiratory resistance in COPD. And they have good correlation with the traditional lung function parameters (FEV1%pred, FVC%pred, FEV1/FVC). Fres has the highest diagnostic accuracy. Comprehensive analysis of R5, R5-R20, Fres and X5 helps to determine the degree of respiratory obstruction in COPD. X5 and Fres can reflect changes in lung tissue compliance. 3D-colored images can visually show the change of respiratory resistance and reactance in COPD.

Proteomic study of benign and malignant pleural effusion.

BACKGROUND: Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion. PURPOSE: This study used proteomics technology to acquire and analyze the protein profiles of the benign and malignant pleural effusion, to seek useful protein biomarkers with diagnostic value and to establish the diagnostic model. METHODS: We chose the weak cationic-exchanger magnetic bead (WCX-MB) to purify peptides in the pleural effusion, used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to obtain peptide expression profiles from the benign and malignant pleural effusion samples, established and validated the diagnostic model through a genetic algorithm (GA) and finally identified the most promising protein biomarker. RESULTS: A GA diagnostic model was established with spectra of 3930.9 and 2942.8 m/z in the training set including 25 malignant pleural effusion and 26 benign pleural effusion samples, yielding both 100 % sensitivity and 100 % specificity. The accuracy of diagnostic prediction was validated in the independent testing set with 58 malignant pleural effusion and 34 benign pleural effusion samples. Blind evaluation was as follows: the sensitivity was 89.6 %, specificity 88.2 %, PPV 92.8 %, NPV 83.3 % and accuracy 89.1 % in the independent testing set. The most promising peptide biomarker was identified successfully: Isoform 1 of caspase recruitment domain-containing protein 9 (CARD9), with 3930.9 m/z, was decreased in the malignant pleural effusion. CONCLUSIONS: This model is suitable to discriminate benign and malignant pleural effusion and CARD9 can be used as a new peptide biomarker.

Different expression of FoxM1 in human benign and malignant pleural effusion.

The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural effusions. FoxM1 expression level could provide evidence for diagnosis and treatment of malignant pleural effusions and lung cancer.