Students test and one-way analysis of variance were used to analyze differences between groups, and a em P /em -value 0.05 was considered to be statistically significant. of miR-34c on NSCLC cell proliferation, apoptosis, and ER stress. Conclusion miR-34c may suppress NSCLC tumors by targeting HMGB1 mRNA, promoting endoplasmic reticulum stress, and increasing ROS levels. Our findings suggest that miR-34c has a role in NSCLC. by use of genetic methods. Numerous studies have shown that numerous miRNAs are expressed in time-dependent and tissue-specific manners.8 Moreover, the expression profiles of miRNAs are dysregulated in multiple human cancers, including NSCLC, liver cancer, breast cancer, and gastric cancer. These findings suggested that miRNAs could be utilized as unique biomarkers for tumor progression. The miR-34 family includes three types: miR-34a, miR-34b, and miR-34c. MiR-34a originates from its own transcript, while miR-34b and miR-34c share a common main transcript.9 In mice, miR-34a was found to be ubiquitously expressed in the brain, while miR-34b and miR-34c were mainly present in lung tissue.9 Recently, miR-34c was revealed to be involved in various human diseases, including neuropathic pain, diabetic corneal neuropathy, and cancers.10C12 However, its role in NSCLC remains largely unclear. Endoplasmic Vitexin reticulum (ER) is an important organelle involved in lipid and protein synthesis. Its function can be disturbed by numerous stimuli, such as hypoxia, dysfunctional protein synthesis, and calcium overload; these disturbances can result in ER stress.13 Previous studies have shown that ER stress plays a critical role in regulating tumor cell apoptosis by activating multiple ER-stress associated proteins, such as inositol requiring protein1 (IRE1), PKR-like ER kinase (PERK), eukaryotic translation initiation factor (eIF), and GADD153.14 High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein that comprises 215 amino acid residues and has three Vitexin distinct domains: two tandem HMG box domains and an acidic C-terminal tail of 30 amino acids.15 HMGB1 was previously reported to participate in the pathogenesis of various human diseases, such as sepsis,16 and cancers,17 by interacting with miRNAs. During ER stress, neurons could release HMGB1 to trigger the initiation of neuron-inflammation and glial activation.18 As for cancer research, HMGB1 has been demonstrated as an oncogene inhibiting cell apoptosis through mediating ER stress,19 accompanying with reactive oxygen species (ROS) production.20 A recent study suggested that ROS induction can lead to cell apoptosis and exert a anti-drug-resistance effect on lung malignancy.21 This might be Vitexin due to the occurrence of DNA damage in lung malignancy induced by ROS generation through mitochondrial membrane potential reprogramming.22C24 In the present study, we investigated the effects of miR-34c and HMGB1 on NSCLC growth and ER stress, as well as the association between miR-34c and HMGB1. RPTOR This was done to better understand the pathogenesis of NSCLC, and identify several novel therapeutic targets for NSCLC. Materials and Vitexin methods NSCLC tissue samples and cell lines A total of 20 pairs NSCLC and adjacent normal tissue samples were collected from Peking University or college Shen Hospital during 2014C2019. Written informed consent was obtained from each subject in advance, and the study protocol was approved by the Ethics Committee of Peking University or college Shen Hospital. The normal human lung cell collection (MRC-5) and five human NSCLC cell lines (A549, H460, H157, H1299, Vitexin and H23) were purchased from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). The cells were maintained at 37 C in RPMI-1640 medium (HyClone Laboratories Inc., Logan, UT, USA) made up of 10% fetal bovine serum (FBS), 1% penicillin/streptomycin, in an atmosphere of 5% CO2 and 95% air flow. Immunohistochemical analysis (IHC) Briefly, fixed samples of NSCLC and normal tissue were embedded with.
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