Lentinan Attenuated the PM2.5 Exposure-Induced Inflammatory Response, Epithelial–Mesenchymal Transition and Migration by Inhibiting the PVT1/miR-199a-5p/caveolin1 Pathway in Lung Cancer

Abstract

PM2.5 plays an important role in the physiological and pathological progression of lung cancer. Lentinan exerts antitumor activity in many kinds of human cancers. Plasmacytoma variant translocation 1 (PVT1) exerts antitumor activity in many kinds of human cancers. However, the role and underlying molecular mechanism of PVT1 in the role of lentinan in PM2.5-exposed lung cancer are still largely unknown. Our study confirmed that PM2.5 exposure induced the production of inflammatory factors, epithelial-mesenchymal transition (EMT) and migration of lung cancer cells. Lentinan exerted antitumor effects by inhibiting the production of inflammatory factors, EMT, and migration of lung cancer cells. Lentinan suppressed PM2.5 exposure-induced cellular progression by inhibiting the PM2.5 exposure-induced elevation of PVT1 expression. PVT1 absorbed miR-199a, and miR-199a inhibited caveolin1 expression and thus formed the PVT1/miR-199a/caveolin1 signaling pathway in lung cancer cells. Our study revealed that silencing of the PVT1/miR-199a/caveolin1 signaling pathway affected the role of lentinan in PM2.5-exposed lung cancer cells. Thus, this study first investigated the role of lentinan in PM2.5-exposed lung cancer cells and further displayed the underlying molecular mechanism, providing a potential treatment for PM2.5-exposed lung cancer.

Identification of Candidate lncRNA and Pseudogene Biomarkers Associated with Carbon-Nanotube-Induced Malignant Transformation of Lung Cells and Prediction of Potential Preventive Drugs

“…In this study, we, for the first time, attempted to screen potential lncRNAs and pseudogenes associated with CNT-induced lung carcinogenesis based on a comprehensive bioinformatics analysis of microarray data of lung cells directly exposed to CNTs without other influencing factors (GSE41178 and GSE561040) and sequencing (TCGA), proteomics (CPTAC) and immunohistochemical data (HPA) of lung cancer patients. Similar to the studies of PM2.5 [ 35 ], nickel [ 36 ] and cadmium [ 37 ] exposure, we also identified that the upregulation of PVT1 and downregulation of MEG3 contributed to the acquisition of tumorigenic phenotypes of human SAECs after CNT exposure. An increase in the expression level of lncRNA ARHGAP5-AS1 and decreases in the expression levels of lncRNA LINC00174, pseudogene MT1JP, MT1L, RPL23AP64, ZNF826P and TMEM198B were newly identified mechanisms in our study to explain the carcinogenic effects of CNTs.…”

“…In recent decades, mounting evidence has supported the idea that environmental pollutants (such as PM2.5 [ 33 , 34 , 35 ], nickel [ 36 ] and cadmium [ 37 , 38 ]) promote the malignant transformation of lung epithelial cells by changing the expression levels of ncRNAs. Dysregulation of ncRNA expression levels was also revealed to be a novel paradigm for interpretation of the toxicology of various nanoparticles [ 39 , 40 , 41 ].…”

“…LncRNAs and pseudogenes were shown to be involved in various cell processes by regulating the expression levels of mRNAs via ceRNA [ 34 , 35 ] or co-expression [ 36 , 37 , 39 , 47 ] mechanisms. Thus, in our study, we constructed ceRNA and co-expression networks to identify the interaction pairs of hub lncRNAs and pseudogenes.…”

Effects of PM2.5 on Chronic Airway Diseases: A Review of Research Progress

“…Ning et al [99] found 13 deregulated miRNAs related to lung cancer in the serum of mice inhaled PM 2.5 for 8 weeks. Moreover, miR-32, miR-582-5p, and miR-199a-5p participate in PM 2.5 -induced EMT and CSC processes, suggesting that miRNAs might be potential targets for lung cancer therapy [94,95,100]. We found that melatonin has an anti-tumor effect by reducing oxidative damage [101].…”

Inhalation of Salvianolic Acid B Prevents Fine Particulate Matter-Induced Acute Airway Inflammation and Oxidative Stress by Downregulating the LTR4/MyD88/NLRP3 Pathway

“…Over recent years, researchers have attempted to prevent and control the cellular and organ damage caused by PM2.5. Some researchers have shown that some natural compounds and traditional Chinese medicines can protect the cell and organ damage induced by PM2.5 both in vitro and in vivo , including calycosin [ 17 ], isovitexin [ 18 ], astaxanthin [ 19 ], curcumin [ 20 ], astragalus [ 21 ], codonopsis pilosula [ 21 ], ophiopogonin [ 22 ], triptolide [ 23 ], astragaloside IV [ 24 ], resveratrol [ 25 ], and lentinan [ 26 ]. All of these studies were carried out in vivo ; drugs were administered systematically, by either oral or injection routes.…”