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- Chen, Baoqing, et al.
(author)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Journal article (peer-reviewed)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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- Li, Yuan, et al.
(author)
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Demographic histories of four spruce (Picea) species of the Qinghai-Tibetan Plateau and neighboring areas inferred from multiple nuclear loci
- 2010
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 27:5, s. 1001-1014
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Journal article (peer-reviewed)abstract
- Nucleotide variation at 12 to 16 nuclear loci was studied in three spruce species from the Qinghai-Tibetan Plateau (QTP), Picea likiangensis, P. wilsonii and P. purpurea, and one species from the Tian Shan mountain range, P. schrenkiana. Silent nucleotide diversity was limited in P. schrenkiana and high in the three species from the QTP, with values higher than in boreal spruce species, despite their much more restricted distributions compared to that of the boreal species. In contrast to European boreal species that have experienced severe bottlenecks in the past, coalescent-based analysis suggests that DNA polymorphism in the species from the QTP and adjacent areas is compatible with the standard neutral model (P. likiangensis, P. wilsonii, P. schrenkiana) or with population growth (P. purpurea). In order to test if P. purpurea is a diploid hybrid of P. likiangensis and P. wilsonii, we used a combination of approaches, including model based inference of population structure, Isolation-with-Migration models and recent theoretical results on the effect of introgression on the geographic distribution of diversity. In contrast to the three other species, each of which was predominantly assigned to a single cluster in the Structure analysis, P. purpurea individuals were scattered over the three main clusters and not, as we had expected, confined to the P. likiangensis and P. wilsonii clusters. Furthermore the contribution of P. schrenkiana was by far the largest one. In agreement with this, the divergence between P. purpurea and P. schrenkiana was lower than the divergence of either P. likiangensis or P. wilsonii from P. schrenkiana. These results, together with previous ones showing that P. purpurea and P. wilsonii share the same haplotypes at both chloroplast and mitochondrial markers, suggest that P. purpurea has a complex origin, possibly involving additional species.
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- Wang, Jiao, et al.
(author)
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Fabrication and whispering gallery resonance of self-rolled up gallium nitride microcavities
- 2017
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In: Thin Solid Films. - : ELSEVIER SCIENCE SA. - 0040-6090 .- 1879-2731. ; 627, s. 77-81
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Journal article (peer-reviewed)abstract
- The C-plane monocrystalline GaN/ZnO thin film epitaxially grows on A-plane sapphire substrate by molecular beam epitaxy (MBE) is revealed by the reflection high-energy electron diffraction (RHEED). The monocrystalline GaN nanomembranes have been rolled up into tubular microstructures as whispering gallery microcavities, which support the whisper gallery modes (WGMs) in the violet and blue regime. The WGMs of the rolled-up monocrystalline GaN devices are tunable with microtube diameter by tuning the strain gradient of the GaN nanomembranes. This approach could help with not only the further development of GaN-based photonic devices, but also the physical understanding of other rolled-up optical microcavities.
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- Yu, Haicheng, et al.
(author)
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Ti3AlC2 coatings deposited by liquid plasma spraying
- 2016
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In: Surface & Coatings Technology. - : ELSEVIER SCIENCE SA. - 0257-8972 .- 1879-3347. ; 299, s. 123-128
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Journal article (peer-reviewed)abstract
- Ti3AlC2 tends to partially decompose into TiC phase during deposition by traditional thermal spray techniques, preventing their use in surface anti-corrosion applications. Here, Ti3AlC2 coatings were synthesized using liquid plasma spraying (LPS). Although the average temperature of particles measured in LPS was higher than 2200 K, enough to decompose Ti3AlC2 phase, the resulting sprayed Ti3AlC2 particles were intact. This is probably due to formation of a protective oxide on the surface in the high-temperature steam. The phase purity of Ti3AlC2 coating was high when using water as solvent, but low with a solvent of a mixture of water and alcohol. Different pH values of the solutions influence the phase purity of Ti3AlC2 coatings. The alkaline solutions show detrimental effect on the conservation of Ti3AlC2 phase. The mechanism of improved structural integrity of Ti3AlC2 phase at high temperature through LPS was revealed by microstructural and compositional analysis. (C) 2016 Elsevier B.V. All rights reserved.
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