This study aimed to explore the role of lncRNA GAS5 in the regulation of the killing effect of NK cells on liver cancer. Compared with a control group, lncRNA GAS5, RUNX3, and NCR1 were down-regulated in NK cells of patients with liver cancer, whereas miR-544 expression was up-regulated in NK cells of patients with liver cancer. Activated NK cells had higher IFN-γ level. Knockdown of GAS5 in activated NK cells decreased IFN-γ secretion, NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 and Huh7 cells. We also proved the interaction of GAS5 and miR-544, and the negative regulation role of GAS5 on miR-544. GAS5 overexpression in activated NK cells increased RUNX3 expression, IFN-γ secretion, the NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 cells, while miR-544 mimic abolished the promotion effect of GAS5 overexpression. Finally, in vivo experiments indicated an inhibition effect of GAS5 in tumor growth. LncRNA GAS5 overexpression enhances the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3.
Deregulation of microRNAs contributes to the abnormal cell growth which is frequently observed in cancer. In the current study, we detected the expression and regulatory relationship between miR‐10a and Lysine‐specific demethylase 4A (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found that miR‐10a levels were significantly decreased in PCa cell lines in comparison with the normal epithelial cell line RWPE‐1. Downregulation of miR‐10a levels was also observed in tumor tissues from PCa patients compared with the adjacent normal tissues. Enhanced expression of miR‐10a inhibited cell proliferation and colony forming capability of PCa cells. In addition, quantitative real‐time polymerase chain reaction and Western blot analysis showed a significant decrease of KDM4A in response to miR‐10a elevation in PCa cells. Using dual luciferase assay, we confirmed that KDM4A was a target gene for miR‐10a. Furthermore, Western blot analysis indicated that miR‐10a overexpression inactivated YAP signaling and suppressed transcription of YAP target genes. Additionally, cell growth arrest and colony forming capacity inhibition induced by miR‐10a overexpression could be reversed by YAP overexpression in PCa cells. More importantly, miR‐10a mimics inhibited PC‐3 tumor growth in nude mice accompanied with a remarkable reduction of KDM4A and YAP expression. In conclusion, our results uncovered a tumor suppressor role of miR‐10a in PCa via negative regulation of KDM4A and its downstream Hippo‐YAP pathway.
Prostate cancer (PCa) is the most frequently diagnosed cancer among men. However, the major modifiable risk factors for PCa are poorly known and its specific mechanism of progression remains unclear. Here we reported that, in prostate cancer cells, the autophagy level was elevated under hypoxic condition, as well as the mRNA and protein level of ATG5, which is an important gene related to autophagy. Furthermore, we found HIF1α could directly bind to the promoter of ATG5 and promote the expression of ATG5 on transcriptional level by luciferase assay and ChIP assay. Intriguingly, overexpression of HIF1α by HIF1α-M could increase tumor size and the effect could be abolished by knockdown ATG5 by si-ATG5 in BALB/cA-nu/nu nude mice. Importantly, HIF1α could also promote the metastasis of PC-3 cells by upregulating the ATG5 and autophagy level and knockdown ATG5 and inhibition autophagy both could abolish the effect of overexpression of HIF1α on the migration of PC-3 cells. Taken together, our results, for the first time, proved that HIF1α could promote the proliferation and migration of PC-3 cells by direct upregulating ATG5 and autophagy level in PC-3 prostate cancer cells. Our findings not only provide new perspective for the relationship between hypoxia and autophagy, but also add new potential therapeutic regimens for the treatment of prostate cancers.
Background: As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use. Methods: In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy. Results: Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs -17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs -17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo. Conclusion:Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.
Mg and Si as the typical dopants for p- and n-type gallium nitride (GaN), respectively, are widely used in GaN-based photoelectric devices. The thermal transport properties play a key role in the thermal stability and lifetime of photoelectric devices, which are of significant urgency to be studied, especially for the Mg- and Si-doped GaN. In this paper, the thermal conductivities of Mg- and Si-doped GaN were investigated based on first-principles calculations and phonon Boltzmann transport equation. The thermal conductivities of Mg-doped GaN are found to be 5.11 and 4.77 W/mK for in-plane and cross-plane directions, respectively. While for the Si-doped GaN, the thermal conductivity reaches the smaller value, which are 0.41 and 0.51 W/mK for in-plane and cross-plane directions, respectively. The decrease in thermal conductivity of Mg-doped GaN is attributed to the combined effect of low group velocities of optical phonon branches and small phonon relaxation time. In contrast, the sharp decrease of the thermal conductivity of Si-doped GaN is mainly attributed to the extremely small phonon relaxation time. Besides, the contribution of acoustic and optical phonon modes to the thermal conductivity has changed after GaN being doped with Mg and Si. Further analysis from the orbital projected electronic density of states and the electron localization function indicates that the strong polarization of Mg-N and Si-N bonds and the distortion of the local structures together lead to the low thermal conductivity. Our results would provide important information for the thermal management of GaN-based photoelectric devices.
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.