Although the inhibitory roles of ursolic acid (UA) have been established in various tumors, its effects on the stemness of non-small cell lung cancer (NSCLC) cells are still unclear. Here, we constructed NSCLC cells with paclitaxel resistance (A549-PR) and showed that A549-PR exhibited a remarkably stronger stemness than the parental A549 cells, which is evident by the increase of spheroid formation capacity, stemness marker expression, and ALDH1 activity. Additionally, UA significantly reduced the stemness and paclitaxel resistance of A549-PR cells. Mechanistic investigations revealed that UA inhibited the miR-149-5p/MyD88 signaling, which is responsible for UA-mediated effects on the stemness of A549-PR cells. Notably, miR-149-5p/MyD88 axis promoted the stemness of A549 cells, while inhibition of this axis attenuated the stemness of A549-PR cells. Therefore, these results suggest that UA could attenuate the stemness and chemoresistance of NSCLC cells through targeting miR-149-5p/MyD88 axis.
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http://dx.doi.org/10.1002/tox.22891 | DOI Listing |
Int J Mol Sci
January 2025
Key Laboratory of Pu-Er Tea Science, Ministry of Education, Yunnan Agricultural University, Heilongtan, North of Kunming, Kunming 650201, China.
Lung cancer is the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and over 60% express wild-type EGFR (WT-EGFR); however, EGFR tyrosine kinase inhibitors (TKIs) have limited effect in most patients with WT-EGFR tumors. In this study, we applied network pharmacology screening and MTT screening of bioactive compounds to obtain one novel grifolic acid that may inhibit NSCLC through the EGFR-ERK1/2 pathway.
View Article and Find Full Text PDFGenes (Basel)
January 2025
Division of Cell and Developmental Genetics, Department of Medicine, Veterans Affairs Medical Center, and the Institute for Human Genetics, University of California, San Francisco, CA 94121, USA.
TSPX is an X-linked tumor suppressor that was initially identified in non-small cell lung cancer (NSCLC) cell lines. However, its expression patterns and downstream mechanisms in NSCLC remain unclear. This study aims to investigate the functions of TSPX in NSCLC by identifying its potential downstream targets and their correlation with clinical outcomes.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally, with a persistently low five-year survival rate of only 14-17%. High rates of metastasis contribute significantly to the poor prognosis of NSCLC, in which inflammation plays an important role by enhancing tumor growth, angiogenesis, and metastasis. Targeting inflammatory pathways within cancer cells may thus represent a promising strategy for inhibiting NSCLC metastasis.
View Article and Find Full Text PDFBiomolecules
December 2024
Cancer Metastasis Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
Metastatic cancer accounts for most cancer-related deaths, and identifying specific molecular targets that contribute to metastatic progression is crucial for the development of effective treatments. Hypoxia, a feature of solid tumors, plays a role in cancer progression by inducing resistance to therapy and accelerating metastasis. Here, we report that CCAAT/enhancer-binding protein beta (C/EBPβ) transcriptionally regulates () and thus promotes migration and invasion of non-small-cell lung cancer (NSCLC) cells under hypoxic conditions.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Department of Pathology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER's protein folding response and Ca homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER.
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