A gene expression signature of tumor proliferation rate in mantle cell lymphoma (MCL) is an overriding molecular predictor of the length of survival following diagnosis. Many strongly proliferative MCL tumors have exceptionally high cyclin D1 mRNA levels and preferentially express short cyclin D1 mRNA isoforms. We demonstrate here that these short mRNAs are cyclin D1a isoforms with truncated 3UTRs, not alternatively spliced cyclin D1b mRNA isoforms. Among 15 MCL tumors with truncated cyclin D1 mRNAs, 7 had genomic deletions in the CCND1 3UTR region. In 3 others, CCND1 contained point mutations that created premature polyadenylation signals, giving rise to 1.5-kb mRNAs lacking most of the 3UTR. Both types of genomic alteration created transcripts lacking mRNA destabilization elements present in the wild-type cyclin D1a mRNA. Premature polyadenylation due to a 3UTR mutation also was present in the Z-138 MCL cell line, which expressed both truncated and full-length cyclin D1a mRNAs. In these cells, the half-life of the short cyclin D1a mRNA was much longer than that of the full-length mRNA. We conclude that alterations of CCND1 3UTR IntroductionMantle cell lymphoma (MCL) comprises about 6% of all nonHodgkin lymphoma and is considered incurable with standard chemotherapy. 1,2 Median survival is approximately 3 years, but survival ranges from less than one year to Ͼ 6 years. The hallmark genetic feature of MCL is the t(11;14) translocation that leads to misexpression of cyclin D1 in the malignant cells. [3][4][5] The t(11;14) is not unique to MCL and occurs also in multiple myeloma. 6 Cyclin D1 is a member of the D-type cyclins that regulate the transition from G 0 /G 1 phase to S phase of the cell cycle. 7 Cyclin D1 is not normally expressed at high levels in lymphoid cells, and its expression from the t(11;14) translocated allele is driven by enhancer elements in the immunoglobulin heavy chain locus. Most t(11;14) translocations take place at the 5Ј end of the cyclin D1 locus, but translocations at the 3Јend of the gene also have been described in some cases. 8 CCND1 has 5 exons, which can be alternatively spliced to create 2 major isoforms, cyclin D1a and D1b. The cyclin D1a isoform is 4.5 kb in length, with a coding region of only 882 bp. The majority of this mRNA consists of 3ЈUTR sequences containing mRNA destabilizing elements. The cyclin D1b isoform lacks exon 5 but retains intron 4, which contains a translation stop codon after 99 bp and a polyadenylation signal less then 300 bp 3Ј from this stop codon. The 1.7-kb cyclin D1b mRNA is found in most tumors and cell lines that express cyclin D1 and encodes a 274 amino acid protein that differs at the C terminus from the 294 amino acid protein encoded by the cyclin D1a mRNA. [9][10][11][12][13] In contrast to cyclin D1a, cyclin D1b is potently transforming in experimental models. 13,14 The relative abundance of the cyclin D1b isoform is reportedly affected by a G/A single nucleotide polymorphism at the last base of exon 4 (position 870, codon 241), which is the...
This paper reports the outcomes of the 2014 Data Fusion Contest organized by the Image Analysis and Data Fusion Technical Committee (IADF TC) of the IEEE Geoscience and Remote Sensing Society (IEEE GRSS). As for previous years, the IADF TC organized a data fusion contest aiming at fostering new ideas and solutions for multisource remote sensing studies. In the 2014 edition, participants considered multiresolution and multisensor fusion between optical data acquired at 20-cm resolution and long-wave (thermal) infrared hyperspectral data at 1-m resolution. The Contest was proposed as a double-track competition: one aiming at accurate landcover classification and the other seeking innovation in the fusion of thermal hyperspectral and color data. In this paper, the results obtained by the winners of both tracks are presented and discussed.Index Terms-Hyperspectral, image analysis and data fusion (IADF), landcover classification, multimodal-, multiresolution-, multisource-data fusion, thermal imaging.
Circular RNAs (circRNAs) play important roles in the initiation and development of different diseases. Here, we detected their role in intervertebral disc (IVD) degeneration. An Arraystar human circular RNA microarray assay was used to detect circRNAs in normal and degenerated human IVD nucleus pulposus (NP) tissues. The role of circ-4099 in IVDD and its mechanism were evaluated by qRT-PCR and gain-of-function/loss-of-function studies. Interaction networks for competing endogenous RNAs (ceRNAs), miRNAs, and miRNA target gene were detected by bioinformatics analysis, RNA immunoprecipitation and luciferase assay. Expression of seventy-two circRNAs were increased by more than twofold in degenerated NP tissues. qRT-PCR showed that the expression of circ-4099 in NP tissues was consistent with that of the array screening. Over-expression of circ-4099 increased the expression of Collagen II and Aggrecan and decreased the secretion of the pro-inflammatory factors IL-1β, TNF-α, and PGE2. TNF-α treatment increased circ-4099 expression in NP cells. NF-κB/MAPK inhibitors or shRNAs abolished the inductive effects of TNF-α on circ-4099 expression. We further demonstrated that circ-4099 was able to function as a “sponge” by competitively binding miR-616-5p, which reversed the suppression of Sox9 by miR-616-5p. We used DNA pull-down and spectrometry experiments to show that TNF-α can promote circ-4099 transcription through upregulation of GRP78. We provide the first evidence that shows circRNAs are differentially expressed in degenerated and normal NP tissues. Circ-4099 may play a role in a protective mechanism and be part of a compensatory response that maintains the synthesis and secretion of the extracellular matrix in NP cells and might be a protective factor in IVD degeneration as well as restore NP cell function.
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