Corrigendum: Downregulation of miR-135b-5p Suppresses Progression of Esophageal Cancer and Contributes to the Effect of Cisplatin.

[This corrects the article DOI: 10.3389/fonc.2021.679348.].

ß-Caryophyllene from Chilli Pepper Inhibits the Proliferation of Non-Small Cell Lung Cancer Cells by Affecting miR-659-3p-Targeted Sphingosine Kinase 1 (SphK1).

BACKGROUND: ß-Caryophyllene is the main ingredient of chilli pepper and used for the prevention of various cancers, while the molecular mechanism for its effects on non-small cell lung cancer (NSCLC) remains unclear. METHODS: NSCLC cell lines A549 and NCI-H1299 were treated with ß-Caryophyllene and miR-659-3p (a potential tumor suppressor) mimic or siRNA. The levels of miR-659-3p, sphingosine kinase 1 (SphK1), apoptotic factors and oxidative stress factors were investigated. RESULTS: ß-Caryophyllene inhibited NSCLC growth, promoted their apoptotic rate, increased the level of miR-659-3p, apoptotic factors (cleaved caspase-3 and BAX), antioxidant factors (SOD, CAT and GPx) and reduced the level of oxidative stress (ROS and NO) and SphK1. miR-659-3p mimic and siRNA affected NSCLC growth, their apoptosis, and biochemical indices. CONCLUSION: ß-Caryophyllene of chilli pepper exerts inhibitory activity in NSCLC cells possibly by affecting miR-659-3p-targeted SphK1.

Downregulation of miR-135b-5p Suppresses Progression of Esophageal Cancer and Contributes to the Effect of Cisplatin.

Esophageal cancer (EC) is one of the commonest human cancers, which accompany high morbidity. MicroRNAs (miRNAs) play a pivotal role in various cancers, including EC. Our research aimed to reveal the function and mechanism of miR-135b-5p. Our research identified that miR-135b-5p was elevated in EC samples from TCGA database. Correspondingly real-time PCR assay also showed the miR-135b-5p is also higher expressed in Eca109, EC9706, KYSE150 cells than normal esophageal epithelial cells (Het-1A). CCK8, Edu, wound healing, Transwell assay, and western blot demonstrated miR-135b-5p inhibition suppresses proliferation, invasion, migration and promoted the apoptosis in Eca109 and EC9706 cells. Moreover, the miR-135b-5p inhibition also inhibited xenograft lump growth. We then predicted the complementary gene of miR-135b-5p using miRTarBase, TargetScan, and DIANA-microT. TXNIP was estimated as a complementary gene for miR-135b-5p. Luciferase report assay verified the direct binding site for miR-135b-5p and TXNIP. Real-time PCR and western blot assays showed that the inhibition of miR-135b-5p remarkably enhanced the levels of TXNIP in Eca109 and EC9706 cells. Furthermore, cisplatin (cis-diamminedichloroplatinum II, DDP) decreased miR-135b-5p expression and increased TXNIP expression. Enhanced expression of miR-135b-5p attenuated the inhibitory ability of cisplatin (cis-diamminedichloroplatinum II, DDP) in Eca109 cells, accompanied by TXNIP downregulation. In conclusion, the downregulation of miR-135b-5p suppresses the progression of EC through targeting TXNIP. MiR-135b-5p/TXNIP pathway contributes to the anti-tumor effect of DDP. These findings may provide new insight into the treatment of EC.

Aloin suppresses lipopolysaccharide-induced acute lung injury by inhibiting NLRP3/NF-κB via activation of SIRT1 in mice.

OBJECTIVE: The purpose of this study was to explore the protective effects and potential mechanisms of aloin on lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: Mice were pretreatment with aloin 1 h before LPS administration. The number of inflammatory cells and the levels of TNF-α and IL-1ß was detected. The lung histopathological changes, wet/dry ratio, MPO activity, GSH, MDA, SOD, and the expression of NF-κB and NLRP3 inflammasome were measured. RESULTS: The results showed that aloin significantly inhibited the number of total cells, neutrophils, and macrophages, as well as the levels of TNF-α and IL-1ß in BALF induced by LPS. In addition, pretreatment with aloin also inhibited LPS-induced lung histopathological injuries, lung wet/dry ratio, MPO activity, and MDA content. The levels of GSH and SOD were decreased by LPS and treatment of aloin could increase the levels of GSH and SOD. To study the protective mechanisms of alion on LPS-induced ALI, the expression of SIRT1, NF-κB and NLRP3 inflammasome were tested. We found that aloin significantly inhibited the activation of NF-κB and NLRP3 inflammasome in ALI induced by LPS. Meanwhile, aloin was found to increase the expression of SIRT1 and inhibition of SIRT1 by EX-527 reversed the protective effects of aloin. CONCLUSIONS: These results suggest that aloin exerts its protective effects on LPS-induced ALI by activation SIRT1, which subsequently results in the suppression of NF-κB and NLRP3 inflammasome.

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.