Colorectal cancer atlas: An integrative resource for genomic and proteomic annotations from colorectal cancer cell lines and tissues

Chisanga, David; Keerthikumar, Shivakumar; Pathan, Mohashin; Ariyaratne, Dinuka; Kalra, Hina; Boukouris, Stephanie; Mathew, Nidhi; Saffar, Haidar Al; Gangoda, Lahiru; Ang, Ching‐Seng; Sieber, Oliver M.; Mariadason, John M.; DasGupta, Ramanuj; Chilamkurti, Naveen; Mathivanan, Suresh

doi:10.1093/nar/gkv1097

Cited by 43 publications

(38 citation statements)

References 26 publications

(30 reference statements)

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“…Together with U2AF65, FUBP1 was identified in a multiprotein complex bound upstream of Tpm2 exon 6b (104), bound a splicing enhancer upstream of DMD exon 39 (32) and a cryptic exon in ATM (105). Importantly, FUBP1 interacts with PUF60 (106) and SRSF3 (107), which both control exon Ab usage (Figure 1C, D). …”

Section: Discussionmentioning

confidence: 99%

Alternative splicing ofU2AF1reveals a shared repression mechanism for duplicated exons

Královičová

Vořechovský

2016

Nucleic Acids Res

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The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab. Each BP lacked canonical uridines at position -2 relative to the BP adenines, with efficient U2 base-pairing interactions predicted only for shifted registers reminiscent of programmed ribosomal frameshifting. The BP cluster was compensated by interactions involving unpaired cytosines in an upstream, EvoFold-predicted stem loop (termed ESL) that binds FUBP1/2. Exon Ab inclusion correlated with predicted free energies of mutant ESLs, suggesting that the ESL operates as a conserved rheostat between long inverted repeats upstream of each exon. The isoform-specific U2AF35 expression was U2AF65-dependent, required interactions between the U2AF-homology motif (UHM) and the α6 helix of U2AF35, and was fine-tuned by exon Ab/3 variants. Finally, we identify tandem homologous exons regulated by U2AF and show that their preferential responses to U2AF65-related proteins and SRSF3 are associated with unpaired pre-mRNA segments upstream of U2AF-repressed 3′ss. These results provide new insights into tissue-specific subfunctionalization of duplicated exons in vertebrate evolution and expand the repertoire of exon repression mechanisms that control alternative splicing.

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Section: Discussionmentioning

confidence: 99%

Alternative splicing ofU2AF1reveals a shared repression mechanism for duplicated exons

Královičová

Vořechovský

2016

Nucleic Acids Res

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“…In 2012 alone, an estimate of 14.1 million people were diagnosed with cancer and around 8.2 million cancer deaths were reported worldwide. Among these, a total of 1.4 million people were estimated to be diagnosed with colorectal cancer (CRC) . Alarmingly, the CRC incidence rates increased to 1.27 million in 2008 .…”

Section: Introductionmentioning

confidence: 99%

Insulin Mediated Activation of PI3K/Akt Signalling Pathway Modifies the Proteomic Cargo of Extracellular Vesicles

Liem

Mathivanan

2017

Proteomics

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Epidemiological studies suggest that diabetes and obesity increases the risk of colorectal cancer (CRC) and lowers the patient survival rate. An important attribute in diabetes and obesity is the presence of high levels of growth factors including insulin in blood which can activate the PI3K/Akt signalling pathway. Dysregulation of PI3K/Akt signalling pathway leads to sustained proliferative signals thereby allowing the cells susceptible to cancer. Extracellular vesicles (EVs), secreted nanovesicles of endocytic origin, are implicated in mediating the transfer of oncogenic cargo in the tumour microenvironment. In this study, CRC cells were treated with insulin to activate PI3K/Akt signaling pathway. Insulin treatment significantly increased the number of EVs secreted by CRC cells. Furthermore, pAkt was exclusively packaged in EVs secreted by PI3K/Akt activated cells. Quantitative proteomics analysis confirmed that the protein cargo of EVs are modified upon activation of PI3K/Akt signaling pathway. Bioinformatics analysis highlighted the enrichment of proteins implicated in cell proliferation in EVs secreted by PI3K/Akt activated cells. Furthermore, incubation of EVs secreted by PI3K/Akt activated cells induced proliferation in recipient CRC cells. These findings suggest that EVs can amplify the signal provided by the growth factors in the tumor microenvironment and hence aid in cancer progression.

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“…APC/C-mediated degradation of cell cycle proteins pathway has been confirmed to involve in colorectal cancer1314. Due to a better understanding of APC/C which involved in mitosis and established a stable G1 phase, the understanding of DNA damage or perturbation of the normal cell cycle had been greatly improved15.…”

Section: Resultsmentioning

confidence: 99%

Identification of cancer risk lncRNAs and cancer risk pathways regulated by cancer risk lncRNAs based on genome sequencing data in human cancers

Wan

Liang

et al. 2016

Sci Rep

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Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The complexity of cancer can be reduced to a small number of underlying principles like cancer hallmarks which could govern the transformation of normal cells to cancer. Besides, the growth and metastasis of cancer often relate to combined effects of long non-coding RNAs (lncRNAs). Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of six types of human cancer patients from The Cancer Genome Atlas (TCGA), and identified six risk pathways and twenty three lncRNAs. In addition, twenty three cancer risk lncRNAs which were closely related to the occurrence or development of cancer had a good classification performance for samples of testing datasets of six cancer datasets. More important, these lncRNAs were able to separate samples in the entire cancer dataset into high-risk group and low-risk group with significantly different overall survival (OS), which was further validated in ten validation datasets. In our study, the robust and effective cancer biomarkers were obtained from cancer datasets which had information of normal-tumor samples. Overall, our research can provide a new perspective for the further study of clinical diagnosis and treatment of cancer.

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Colorectal cancer atlas: An integrative resource for genomic and proteomic annotations from colorectal cancer cell lines and tissues

Cited by 43 publications

References 26 publications

Alternative splicing ofU2AF1reveals a shared repression mechanism for duplicated exons

Alternative splicing ofU2AF1reveals a shared repression mechanism for duplicated exons

Insulin Mediated Activation of PI3K/Akt Signalling Pathway Modifies the Proteomic Cargo of Extracellular Vesicles

Identification of cancer risk lncRNAs and cancer risk pathways regulated by cancer risk lncRNAs based on genome sequencing data in human cancers

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