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1.
Biomed Pharmacother ; 142: 111967, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34467896

ABSTRACT

miR-34, whose mimic was used on phase I clinical trial, has been extensively reported since its dysfunction in various cancers including non-small-cell lung cancer (NSCLC). However, the roles of miR-34 family members in the progression of lung squamous carcinoma (SCC) in patients who have occupational-exposure experience are unclear yet. Here, we comprehensively investigated the expression levels of miR-34 family members in SCC patients and compared the roles of them in SCC in vitro and vivo. The results showed that the average levels of miR-34a and miR-34b/c were decreased in patients. The analysis of miR-34a to miR-34b/c levels in patients graded different stages or metastases or recurrence showed that miR-34b/c was reduced earlier and more significantly than miR-34a. In vitro assays demonstrated that both miR-34a and miR-34b/c inhibits SCC cells proliferation, migration and invasion via Notch1 pathway, while miR-34b/c effects more than miR-34a does. As miR-34a was significantly decreased in cancer recurrence, the further analysis of relationship between miR-34a and stem cell adhesion molecular CD44 showed that miR-34a was significantly correlated with CD44 levels in patients. Knockdown of CD44 significantly blocked miR-34a mediated inhibition of cell migration and invasion. Treating the purified CD44hi cells with miR-34 overexpression lentivirus inhibited the tumor outgrowth. By contrast, anti-miR-34 facilitated tumor development of CD44low cells. Our study showed that miR-34 family members are negative regulator for SCC development, even though the inhibition is mediated by multiple and complicated signal pathways, which provides theoretical basis for SCC treatment and a biomarker candidate for SCC prognosis.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Hyaluronan Receptors/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Animals , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Gene Knockdown Techniques , Humans , Lung Neoplasms/pathology , Male , Mice , Mice, SCID , Neoplasm Staging , Occupational Exposure/adverse effects , Prognosis , Xenograft Model Antitumor Assays
2.
Ecotoxicology ; 23(4): 665-73, 2014 May.
Article in English | MEDLINE | ID: mdl-24510466

ABSTRACT

Pollution caused by petroleum is one of the most serious problems worldwide. To better understand the toxic effects of petroleum-contaminated soil on the microflora and phytocommunity, we conducted a comprehensive field study on toxic effects of petroleum contaminated soil collected from the city of Daqing, an oil producing region of China. Urease, protease, invertase, and dehydrogenase activity were significantly reduced in microflora exposed to contaminated soils compared to the controls, whereas polyphenol oxidase activity was significantly increased (P < 0.05). Soil pH, electrical conductivity, and organic matter content were correlated with total petroleum hydrocarbons (TPHs) and a correlation (P < 0.01) existed between the C/N ratio and TPHs. Protease, invertase and catalase were correlated with TPHs. The Vicia faba micronucleus (MN) test, chromosome aberrant (CA) analyses, and the mitotic index (MI) were used to detect genotoxicity of water extracts of the soil. Petroleum-contaminated samples indicated serious genotoxicity to plants, including decreased index level of MI, increased frequency of MN and CA. The combination of enzyme activities and genotoxicity test via Vicia faba can be used as an important indicator for assessing the impact of TPH on soil ecosystem.


Subject(s)
Petroleum Pollution/adverse effects , Soil Pollutants/adverse effects , China , Enzymes/analysis , Micronucleus Tests , Risk Assessment , Soil/chemistry , Vicia faba
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