BackgroundmiR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported.MethodsThe expression level of miR-203a-3p in human NPC tissues and cell lines was detected via real-time PCR (RT-PCR). Cell proliferation, migration and invasion were assessed in vitro by MTT, colony formation and transwell assay, respectively. The function of miR-203a-3p in vivo was detected through NPC xenograft tumor growth and lung metastatic mice model. Dual-luciferase reporter assay was used to identify the direct target of miR-203a-3p.ResultsThe expression of miR-203a-3p was decreased in NPC tissues and cell lines in comparison with normal nasopharyngeal tissues and cell line. Ectopic expression of miR-203a-3p inhibited while inhibiting miR-203a-3p expression increased NPC cell proliferation, migration and invasion in vitro. MR-203a-3p overexpression suppressed xenograft tumor growth and lung metastasis in vivo. LASP1 was identified as a direct target of miR-203a-3p, which was confirmed by real-time PCR and western blotting assay. Ectopic expression of LASP1 partially reversed miR-203a-3p-mediated inhibition on proliferation, migration and invasion in NPC cells.ConclusionCollectively, miR-203a-3p suppresses tumor growth and metastasis through targeting LASP1 in NPC. The newly identified miR-203a-3p/LASP1 pathway provides further insights into the initiation and progression of NPC, which may represent a novel therapeutic target for NPC.
Populus, a core genus of Salicaceae, plays a significant ecological role as a source of pioneer species in boreal forests. However, interspecific hybridization and high levels of morphological variation among poplars have resulted in great difficulty in classifying species for systematic and comparative evolutionary studies. Here, we present phylogenetic analyses of 24 newly sequenced Populus plastomes and 36 plastomes from GenBank, which represent seven genera of Salicaceae, in combination with a matrix of eighteen morphological characters of 40 Populus taxa to reconstruct highly supported relationships of genus Populus. Relationships among the 60 taxa of Salicaceae strongly supported two monophyletic genera: Populus and Salix. Chosenia was nested within the genus Salix, and five clades within Populus were divided. Clade I included the three taxa P. euphratica, P. pruinosa, and P. ilicifolia. Clade II contained thirteen taxa [P. adenopoda, P. alba, P. bolleana, P. davidiana, P. hopeiensis, P. nigra, P. qiongdaoensis, P. rotundifolia, P. rotundifolia var. duclouxiana, P. tremula, P. tremula × alba, P. tomentosa, and P. tomentosa (NC)]. Clade III included the ten taxa P. haoana, P. kangdingensis, P. lasiocarpa, P. pseudoglauca, P. qamdoensis, P. schneideri, P. simonii, P. szechuanica, P. szechuanica var. tibetica, and P. yunnanensis. Clade IV included P. cathayana, P. gonggaensis, P. koreana, P. laurifolia, P. trinervis, P. wilsonii, and P. xiangchengensis. The last clade comprised P. angustifolia, P. balsamifera, P. deltoides, P. deltoides × nigra, P. fremontii, P. mexicana, and P. trichocarpa. This phylogeny is also supported by morphological traits, including bark smoothness, bud size, petiole shape, leaf inflorescence, male anther length and male anther tip.
PurposeThe purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC).Materials and MethodsThe endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.ResultsZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/β-catenin signaling pathway.ConclusionOur data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/β-catenin pathway to induce EMT in NPC.
BACKGROUND:The major clinical obstacle that limits the long-term benefits of treatment with osimertinib (AZD9291) in patients with epidermal growth factor receptor-mutant non-small cell lung cancer is the development of acquired resistance. Therefore, effective strategies that can overcome acquired resistance to osimertinib are urgently needed. The authors' current efforts in this direction have identified LBH589 (panobinostat), a clinically used histone deacetylase inhibitor, as a potential agent in overcoming osimertinib resistance. METHODS: Cell growth and apoptosis in vitro were evaluated by measuring cell numbers and colony formation and by detecting annexin V-positive cells and protein cleavage, respectively. Drug effects on tumor growth in vivo were assessed with xenografts in nude mice. Alterations of tested proteins in cells were monitored with Western blot analysis. Gene knockout was achieved using the CRISPR/ Cas9 technique. RESULTS: The combination of LBH589 and osimertinib synergistically decreased the survival of different osimertinibresistant cell lines, including those harboring C797S mutations, with greater inhibition of cell colony formation and growth. The combination enhanced the induction of apoptosis in osimertinib-resistant cells. Importantly, the combination effectively inhibited the growth of osimertinib-resistant xenograft tumors in nude mice. Mechanistically, the combination of LBH589 and osimertinib enhanced the elevation of Bim in osimertinib-resistant cells. Knockout of Bim in osimertinib-resistant cells substantially attenuated or abolished apoptosis enhanced by the LBH589 and osimertinib combination. These results collectively support a critical role of Bim elevation in the induction of apoptosis of osimertinib-resistant cells for this combination. CONCLUSIONS: The current findings provide strong preclinical evidence in support of the potential for LBH589 to overcome osimertinib resistance in the clinic.
Species of the genus Populus, which is widely distributed in the northern hemisphere from subtropical to boreal forests, are among the most commercially exploited groups of forest trees. In this study, the complete chloroplast genomes of five Populus species (Populus cathayana, P. kangdingensis, P. pseudoglauca, P. schneideri, and P. xiangchengensis) were compared. The chloroplast genomes of the five Populus species are very similar. The total chloroplast genome sequence lengths for the five plastomes were 156,789, 156,523, 156,512, 156,513, and 156,465 bp, respectively. A total of 130 genes were identified in each genome, including 85 protein-coding genes, 37 tRNA genes and eight rRNA genes. Seven genes were duplicated in the protein-coding genes, whereas 11 genes were duplicated in the RNA genes. The GC content was 36.7% for all plastomes. We analyzed nucleotide substitutions, small inversions, simple sequence repeats and long repeats in the chloroplast genomes and found nine divergence hotspots (ccsA+ccsA-ndhD, ndhC-trnV, psbZ-trnfM, trnG-atpA, trnL-ndhJ, trnR-trnN, ycf4-cemA, ycf1, and trnR-trnN), which could be useful molecular genetic markers for future population genetic and phylogenetic studies. We also observed that two genes (rpoC2 and rbcL) were subject to positive selection. Phylogenetic analysis based on whole cp genomes showed that P. schneideri had a close relationship with P. kangdingensis and P. pseudoglauca, while P. xiangchengensis was a sister to P. cathayana.
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.