Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a multifunctional cytokine that signals between the cell and the extracellular matrix. Periostin plays an important role in tumor development and is involved in carcinoma cell epithelial-mesenchymal transition (EMT), whereby mature epithelial cells undergo phenotypic morphological changes and become invasive, motile cells. Here, we discuss the molecular mechanisms involved in periostin-induced promotion of EMT in lung cancer cells. Online TCGA datasets demonstrate the prognostic relevance of periostin in lung cancer; a higher periostin level correlates with poor overall survival. Similarly, our IHC results show that high periostin expression is positively correlated with the EMT markers Snail and Twist, as well as stage of lung cancer. We found that recombinant periostin induces the EMT phenotype in lung cancer cells through the p38/ERK pathway, while pretreatment with chemical inhibitors prevented periostin-induced EMT induction. Moreover, we found that periostin regulates EMT by repressing microRNA-381 (miR-381) expression, which targets both Snail and Twist. Using the miR-381 mimic, we dramatically reversed periostin-induced Snail and Twist expression. Furthermore, periostin knockdown dramatically affected EMT markers and cell migration potential. The role of periostin in lung cancer progression is elucidated by the in vivo mouse model. Our findings indicate that changes in periostin expression in lung cancer may serve as a therapeutic target for the treatment of lung cancer metastasis.
Lung cancer is one of the most frequently diagnosed malignancies and is associated with a poor survival rate in the Chinese Han population. Analysis of genetic variants could lead to improvements in prognosis following lung cancer therapy. High-mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein found in eukaryotic cells that participates in several biological functions including immune response, cell survival, apoptosis and cancer development. We investigated the effects of HMGB1 gene polymorphisms on the risk of lung cancer progression in a Chinese Han population. Our sample of 751 participants included 372 patients with lung cancer and 379 healthy controls. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene were examined by real-time polymerase chain reaction (RT-PCR). We found that the CT or CC+CT heterozygotes of the HMGB1 rs1045411 polymorphism reduced the risks for lung cancer, while the G/T/C haplotypes of three HMGB1 SNPs (rs1360485, rs1045411 and rs2249825) also reduced the risk for lung cancer by almost half (0.486-fold). The current study is the first to examine the risk factors associated with HMGB1 SNPs in lung cancer development in the Chinese Han population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.