MiPanda: A Resource for Analyzing and Visualizing Next-Generation Sequencing Transcriptomics Data

Niknafs, Yashar S.; Pandian, Balaji; Gajjar, Tilak; Gaudette, Zach; Wheelock, Kevin M.; Maz, Mitra P.; Achar, Rohan K.; Song, Melinda R.; Massaro, Cory; Cao, Xuhong; Chinnaiyan, Arul M.

doi:10.1016/j.neo.2018.09.001

Cited by 20 publications

(18 citation statements)

References 19 publications

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“…SALL2 gene counts across normal/tumor including associated statistics ( p -value calculation) in tumor/normal gene quantifications were downloaded from Michigan Portal for the Analysis of NGS data portal 2 ( Niknafs et al, 2018 ), which combines Transcript per million values (TPM) from next-generation sequencing datasets provided from TCGA, ICGC, GTEX, and CCLE consortia ( Zhang et al, 2011 ; Barretina et al, 2012 ; Cancer Genome Atlas Research Network et al, 2013 ; GTEx Consortium, 2013 ). SALL2 isoform-specific counts were obtained from ISOexpresso server, containing spliced RNA-seq data obtained from TCGA ( Yang et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

“…This transcript diversity is essential for regulating various biological processes ( Pozner et al, 2007 ; Gabut et al, 2011 ; Schaub and Glasmacher, 2017 ), and aberrant expression of transcripts is associated with diseases such as cancer ( Mayr and Bartel, 2009 ; Xiong et al, 2015 ; Sendoel et al, 2017 ). The availability of high-quality tumor RNA sequencing provided by international consortia such as the Cancer Genome Atlas (TCGA) ( Cancer Genome Atlas Research Network et al, 2013 ), International Cancer Genome Consortium (ICGC) ( Zhang et al, 2011 ), Genotype-Tissue Expression (GTEX) ( GTEx Consortium, 2013 ) and Broad Institute Cancer Cell Line Encyclopedia (CCLE) ( Barretina et al, 2012 ), enables robust characterization and discovery of cancer/tissue-specific isoforms, which can be explored in various ways and can be intersected with next generation sequencing data ( Niknafs et al, 2018 ). Additionally, chromatin immunoprecipitation sequencing (ChIP-seq) can be used for inferring regulatory pathways and the control of gene expression under disease or in a given cell-type/tissue.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks

et al. 2021

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The SALL2 transcription factor, an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation. In disease, SALL2 is associated with eye, kidney, and brain disorders, but mainly is related to cancer. Some studies support a tumor suppressor role and others an oncogenic role for SALL2, which seems to depend on the cancer type. An additional consideration is tissue-dependent expression of different SALL2 isoforms. Human and mouse SALL2 gene loci contain two promoters, each controlling the expression of a different protein isoform (E1 and E1A). Also, several improvements on the human genome assembly and gene annotation through next-generation sequencing technologies reveal correction and annotation of additional isoforms, obscuring dissection of SALL2 isoform-specific transcriptional targets and functions. We here integrated current data of normal/tumor gene expression databases along with ChIP-seq binding profiles to analyze SALL2 isoforms expression distribution and infer isoform-specific SALL2 targets. We found that the canonical SALL2 E1 isoform is one of the lowest expressed, while the E1A isoform is highly predominant across cell types. To dissect SALL2 isoform-specific targets, we analyzed publicly available ChIP-seq data from Glioblastoma tumor-propagating cells and in-house ChIP-seq datasets performed in SALL2 wild-type and E1A isoform knockout HEK293 cells. Another available ChIP-seq data in HEK293 cells (ENCODE Consortium Phase III) overexpressing a non-canonical SALL2 isoform (short_E1A) was also analyzed. Regardless of cell type, our analysis indicates that the SALL2 long E1 and E1A isoforms, but not short_E1A, are mostly contributing to transcriptional control, and reveals a highly conserved network of brain-specific transcription factors (i.e., SALL3, POU3F2, and NPAS3). Our data integration identified a conserved molecular network in which SALL2 regulates genes associated with neural function, cell differentiation, development, and cell adhesion between others. Also, we identified PODXL as a gene that is likely regulated by SALL2 across tissues. Our study encourages the validation of publicly available ChIP-seq datasets to assess a specific gene/isoform’s transcriptional targets. The knowledge of SALL2 isoforms expression and function in different tissue contexts is relevant to understanding its role in disease.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks

et al. 2021

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“…We explored the online portal MiPanda to find Plexin-B3 expression in the normal pancreas and the pancreatic tumor samples. The MiPanda portal contained next-generation sequencing data for 419 pancreatic cancer cases [ 44 ]. We also utilized the GEPIA portal for a survival analysis of pancreatic ductal adenocarcinoma patients with respect to Plexin-B3 expression [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Plexin-B3 Regulates Cellular Motility, Invasiveness, and Metastasis in Pancreatic Cancer

Saxena

Prajapati

Goel

et al. 2021

Cancers

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The Plexins family of proteins are well-characterized transmembrane receptors of semaphorins, axon guidance cue molecules, that mediate the cell attraction or repelling effects for such cues. Plexins and their ligands are involved in numerous cellular activities, such as motility, invasion, and adhesion to the basement membrane. The detachment of cells and the gain in motility and invasion are hallmarks of the cancer metastasis cascade, thus generating interest in exploring the role of plexins in cancer metastasis. Semaphorin–plexin complexes can act as tumor promoters or suppressors, depending upon the cancer type, and are under investigation for therapeutic purposes. Our group has identified Semaphorin-5A (SEMA5A)/Plexin-B3 as an attractive targetable complex for pancreatic cancer (PC) metastasis. However, our understanding of the Plexin-B3 function and pathological expression in PC is limited, and our present study delineates the role of Plexin-B3 in PC malignancy. We examined the pathological expression of Plexin-B3 in PC tumors and metastasis using a human tissue microarray, disease progression model of PDX-Cre-Kras(G12D) (KC) mice, and different metastatic sites obtained from the KrasG12D; Trp53R172H; Pdx1-Cre (KPC) mice model. We observed a higher Plexin-B3 expression in PC tumor cores than the normal pancreas, and different metastatic sites were positive for Plexin-B3 expression. However, in the KC mice model, the Plexin-B3 expression increased initially and then decreased with the disease progression. Next, to evaluate the functional role of Plexin-B3, we utilized T3M-4- and CD18/HPAF-Control and -Plexin B3 knockdown cells for different in vivo and in vitro studies. The knockdown of Plexin-B3 enhanced the in vitro cellular migration, invasiveness, and impaired colony formation in three-dimensional culture, along with an increase in cellular spread and remodeling of the actin filaments. We also observed a higher metastasis in nude mice injected with T3M-4- and CD18/HPAF-shPlexin-B3 cells compared to their respective control cells. Furthermore, we observed a lower number of proliferating Ki-67-positive cells and higher ALDH1-A1-positive cells in the tumors formed by Plexin-B3 knockdown cells compared to tumors formed by the control cells. Together, our data suggest that the loss of Plexin-B3 is associated with the interference of cell division machinery and the induction of stem cell-like characteristics in PC cells.

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“…1i). We also, analyzed the coexpression of Nup62 and Nup88 in oral cancers in a collection of available datasets at MiPanda 28 . The Nup62 and Nup88 transcript levels are optimal in normal tissues, but significant overexpression of both these transcripts was common in primary tumors.…”

Section: Nup88 and Nup62 Are Overexpressed In Head And Neck Cancermentioning

confidence: 99%

Overexpressed Nup88 stabilized through interaction with Nup62 promotes NFκB dependent pathways in cancer

Singh

Samaiya

Mishra

2020

Preprint

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Nuclear pores control nucleo-cytoplasmic trafficking and directly or indirectly regulate vital cellular processes. Nup88, important for Crm1 mediated nuclear export process, is overexpressed in many cancers. A positive correlation exists between progressive stages of cancer and Nup88 expression. However, links between Nup88 overexpression and head and neck cancer are insignificant, and mechanistic details are non-existent. Here, we report that Nup88 exhibits positive correlation in head and neck cancer in addition to elevated Nup62 levels. We demonstrate that Nup88 interacts with Nup62 in a cell-cycle and glycosylation independent manner. The overexpression of Nup88 or Nup62 imparts proliferation and migration advantages to cells. We further report that the interaction with Nup62 stabilizes Nup88 by inhibiting proteasome-mediated degradation of overexpressed Nup88. Overexpressed Nup88 is stabile and partly inside the nucleus and can interact with NFB (p65). Nup88 overexpression induces proliferative and inflammatory responses downstream of p65. Altogether, we suggest that simultaneous overexpression of Nup62 and Nup88 in head and neck cancer stabilizes overexpressed Nup88. Stable Nup88 interacts with p65 and induces inflammatory, proliferative, and migratory advantages to cells, which perhaps is the underlying mechanism driving tumorigenic transformations.

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MiPanda: A Resource for Analyzing and Visualizing Next-Generation Sequencing Transcriptomics Data

Cited by 20 publications

References 19 publications

Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks

Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks

Plexin-B3 Regulates Cellular Motility, Invasiveness, and Metastasis in Pancreatic Cancer

Overexpressed Nup88 stabilized through interaction with Nup62 promotes NFκB dependent pathways in cancer

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