Identification Invasion-Related Long Non-Coding RNAs in Lung Adenocarcinoma and Analysis of Competitive Endogenous RNA Regulatory Networks.

Background: Cell invasion plays a vital role in cancer development and progression. Aberrant expression of long non-coding RNAs (lncRNAs) is also critical in carcinogenesis. However, the prognostic value of invasion-related lncRNAs in lung adenocarcinoma (LUAD) remains unknown. Methods: Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and microRNAs (DEmiRNAs) were between LUAD and control samples. Pearson correlation analyses were performed to screen for invasion-related DElncRNAs (DEIRLs). Univariate and multivariate Cox regression algorithms were applied to identify key genes and construct the risk score model, which was evaluated using receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA) was used to explore the underlying pathways of the risk model. Moreover, an invasion-related competitive endogenous RNA (ceRNA) regulatory network was constructed. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of prognostic lncRNAs in the LUAD and control samples. Results: A total of 45 DElncRNAs were identified as DEIRLs. RP3-525N10.2, LINC00857, EP300-AS1, PDZRN3-AS1, and RP5-1102E8.3 were potential prognostic lncRNAs, the expression of which was verified by RT-qPCR in LUAD samples. Both the risk score model and nomogram used the prognostic lncRNAs. ROC curves showed the risk score model had moderate accuracy and the nomogram had high accuracy in predicting patient prognosis. GSEA results indicated that the risk score model was associated with many biological processes and pathways relevant to cell proliferation. A ceRNA regulatory network was constructed in which PDZRN3-miR-96-5p-CPEB1, EP300-AS1-miR-93-5p-CORO2B, and RP3-525N10.2-miR-130a-5p-GHR may be key invasion-related regulatory pathways in LUAD. Conclusion: Our study identified five novel invasion-related prognostic lncRNAs (RP3-525N10.2, LINC00857, EP300-AS1, PDZRN3-AS1, and RP5-1102E8.3) and established an accurate model for predicting the prognosis of patients with LUAD. These findings enrich our understanding of the relationships between cell invasion, lncRNAs, and LUAD and may provide novel treatment directions.

ROCK2 mediates the proliferation of pulmonary arterial endothelial cells induced by hypoxia in the development of pulmonary arterial hypertension.

It has been reported that RhoA activation and Rho-kinase (ROCK) expression are increased in chronic hypoxic lungs, and the long-term inhibition of ROCK markedly improves the survival of patients with pulmonary arterial hypertension (PAH). However, whether Rho-kinase α (ROCK2) participates in regulation of the growth of pulmonary arterial endothelial cells (PAECs) remains unknown. The aim of the present study was to investigate the effect of hypoxia on the proliferation of PAECs and the role of ROCK2 in the underlying mechanism. The results of western blotting and reverse transcription-quantitative polymerase chain reaction analysis showed that hypoxia increased the activity and expression of ROCK2 in PAECs, and the stimulating effects of hypoxia on the proliferation of PAECs were attenuated by either the ROCK inhibitor Y27632 or transfection with ROCK2 small interfering RNA. Moreover, analysis of cyclin A and cyclin D1 mRNA expression indicated that ROCK2 mediates the cell cycle progression promoted by hypoxia. These results indicate that hypoxia promotes the proliferation of pulmonary arterial endothelial cells via activation of the ROCK2 signaling pathway.