Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer.

OBJECTIVE: To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). METHODS: The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. RESULTS: p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. CONCLUSIONS: Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

LncRNA LINC00163 upregulation suppresses lung cancer development though transcriptionally increasing TCF21 expression.

Long noncoding RNAs (lncRNAs) have been illustrated as vital molecules in regulating human cancer by emerging evidence. LINC00163 is a novel lncRNA without functional definition. In this study, we investigated its role in the tumorigenesis of lung cancer. The results showed that LINC00163 level was significantly downregulated in lung cancer tissues and cell lines by bioinformatics and qRT-PCR analyses. Notably, we observed that LINC00163 expression was lower in metastatic tissues than in non-metastatic cases. Furthermore, higher expression of LINC00163 in patients with lung cancer predicted better prognosis. Gain-of-function assays illustrated that upregulation of LINC00163 dramatically suppressed the proliferation, migration and invasion of lung cancer cells in vitro, whereas promoting apoptosis. Consistently, LINC00163 overexpression impaired tumor propagation in vivo. Mechanical study revealed that LINC00163 recruited ARID1A to the promoter of TCF21 and initiated its expression. In conclusion, we concluded that LINC00163/ARID1A/TCF21 regulatory loop modulated the development of lung cancer, providing a new insight on the mechanism underlying lung cancer progression.

Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress.

Acute lung injury (ALI) is a common severe clinical syndrome in intensive care unit. Inflammation has been reported to play a critical role in the development of ALI. Cordycepin, an active component isolated from Cordyceps militaris, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of cordycepin on LPS-induced ALI remain unclear. Therefore, in the present study, we assessed whether cordycepin could attenuate ALI induced by LPS. The mice were conditioned with cordycepin 1h before intranasal instillation of LPS. Lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production were detected. The expression of NF-κB p65, I-κB, Nrf2, and HO-1 were detected by western blot analysis. We found that LPS significantly increased lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production. However, the increases were significantly inhibited by treatment of cordycepin. LPS-induced NF-κB activation was also suppressed by cordycepin. In addition, cordycepin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, our results demonstrated that cordycepin could attenuate LPS-induced ALI effectively, probably due to inhibition of inflammation and oxidative stress.