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- Afzal, Wasif, et al.
(författare)
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Program committee for icse 2018 posters track
- 2018
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Ingår i: Proceedings / International Conference of Software Engineering. - : IEEE Computer Society. - 0270-5257 .- 1558-1225. ; Part F137351
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)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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- Valstar, A., et al.
(författare)
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Heat-set bovine serum albumin-sodium dodecyl sulfate gels studied by fluorescence probe methods, NMR, and light scattering
- 2001
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 17:11, s. 3208-3215
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Tidskriftsartikel (refereegranskat)abstract
- In this work, concentrated protein-surfactant solutions and their corresponding heat-set gels; were studied by fluorescence probe methods, NMR, and light scattering. Bovine serum albumin (BSA) was used as the protein, and sodium dodecyl sulfate (SDS) as the surfactant. Heating concentrated BSA solutions gives turbid gels. Heat-setBSA-SDS gels are transparent. From fluorescence measurements it was concluded that SDS forms micelle-like clusters on BSA, both in solution and in the corresponding heat-set gel. Aggregation numbers were found to be similar in solution and gel. Also, I-1/I-3 values in solution and gel were similar. H-2 NMR relaxation measurements of specifically deuterated SDS at the ct-carbon position next to the headgroup were performed, and the longitudinal relaxation rates R-1 were found to be the same in solution and gel. High values for the transverse relaxation rate R-2 (indicating slow motions of SDS bound to large aggregates) were obtained, and the largest R-2 value was found for the gel. Dynamic light scattering on BSA-SDS gels was used to obtain the correlation length xi, which defines a mean distance between two points of entanglements. The decrease of xi with increasing [SDS]/[BSA] molar ratio was explained by the size of the BSA-SDS complex and the possibility that micelle-like structures might form cross-links between different BSA molecules. With static light scattering the extent of inhomogeneities in BSA and BSA-SDS gels was found to decrease with increasing SDS concentration. Also, the gel region in the ternary phase diagram BSA-SDS-3.1 mM NaN3 at room temperature and constant pressure (1 atm) was determined.
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