hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles

Fischl, Harry; Neve, Jonathan; Wang, Zhiqiao; Patel, Radhika; Louey, Alastair; Tian, Bin; Furger, André

doi:10.1093/nar/gkz461

Cited by 91 publications

(96 citation statements)

References 44 publications

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“…Several processes could be responsible, such as posttranscriptional modifications, protein degradation, secretion via exocytosis or alterations in subcellular protein localization. For example a recent paper has reported that NAP1L1 undergoes alternative cleavage and polyadenylation in the more advanced stages of CRC (38). The full length isoform of NAP1L1 was overrepresented in the cytoplasmic fraction of a CRC cell line which had a more metastatic phenotype.…”

Section: Discussionmentioning

confidence: 99%

NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation

et al. 2020

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Results: Nap1l1 mRNA expression was increased in mouse small intestine following Apc deletion in a Myc dependant manner and was also increased in human CRC samples. Immunohistochemical NAP1L1 expression was decreased in human CRC samples relative to matched adjacent normal colonic tissue. In a separate cohort of 75 CRC patients, we found a strong correlation between NAP1L1 nuclear expression and overall survival in those patients who had stage III and IV cancers. Conclusion: NAP1L1 expression is increased in the mouse small intestine following Apc inactivation and its expression is also altered in human CRC. Immunohistochemical NAP1L1 nuclear expression correlated with overall survival in a cohort of CRC patients. Further studies are now required to clarify the role of this protein in CRC.

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Section: Discussionmentioning

confidence: 99%

NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation

et al. 2020

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“…12q24 chromosomal region gain tumours (where it is located) [112]. RAN also promotes AURKA activity, with Schnepp and colleagues suggesting that RAN overexpression could be targeted by aurora kinase inhibitors.…”

Section: Rbps Associated With High-risk Patient Death: Aff2 and Bard1mentioning

confidence: 99%

“…HNRNPC was ranked 30 in our Kaplan scan analyses. Overexpression of HNRNPC has a critical role in the establishment of alternative cleavage and polyadenylation profiles, which are characteristic of metastatic colon cancer cells [112]. Furthermore, the loss of HNRNPC strongly reduces the abundance of BRCA1, BRCA2, RAD51 and BRIP1 due to aberrant splicing effects [113].…”

Section: Rbps Associated With High-risk Patient Death: Aff2 and Bard1mentioning

confidence: 99%

“…Of the top 30 mRNAs, RAN is perhaps the most reported RBP in cancer. In neuroblastoma, RAN expression is promoted by LIN28B and RAN expression is higher in 12q24 chromosomal region gain tumours (where it is located) [112]. RAN also promotes AURKA activity, with Schnepp and colleagues suggesting that RAN overexpression could be targeted by aurora kinase inhibitors.…”

Section: One-third Of Rbps Have Prognostic Value In Neuroblastoma Inmentioning

confidence: 99%

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Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Bell

Hagemann

Holien

et al. 2020

IJMS

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Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.

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“…The TAPA event introduces two or more poly(A) sites to the 3′ UTR of a gene which is distributed across a wide variety of cancers and modulates the sensitivity of certain anticancer drugs [12,13]. The shift of TAPA events shows a cancer-specific and cell organelle-specific mode [14]. It was reported that the APA-guided shortening of NET1 gene 3' UTR enhanced mRNA transcriptional activity and promoted the metastasis of gastric cancer cells [15].…”

Section: Introductionmentioning

confidence: 99%

Identification of novel alternative splicing events associated with tumorigenesis, protein modification, and immune microenvironment in early-onset gastric cancer

Zhang

Zhu

2020

Preprint

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BackgroundAlternative splicing (AS), e.g. tandem alternative polyadenylation (TAPA), has emerged as major post-transcriptional modification events in human disease. However, the roles of AS and TAPA in early-onset gastric cancer (EOGC) have not been revealed.MethodsThe global AS profiles of 80 EOGC patient samples from the European Nucleotide Archive (PRJNA508414) were analyzed. The EOGC-specific AS events (ESASs) were identified in both EOGC and adjacent non-tumor tissues. Functional enrichment analysis, Splicing network, Alternative Polyadenylation (APA) core factor network, and cell abundancy analysis were performed. Furthermore, the landscapes of AS events in the varied subtypes of EOGC patients, including various protein modifications and viral infections, were evaluated.ResultsOverall, 66,075 AS events and 267 ESASs were identified in EOGC. In these events, 4809 genes and 6152 gene isoforms were found to be aberrantly expressed in EOGC. The Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses showed that significant pathway alterations might exist in these AS events, genes, and gene isoforms. Moreover, the Protein-protein interaction (PPI) network analysis revealed that UBC, NEK2, EPHB2, and DCTN1 genes were the hub genes in the AS events in EOGC. The immune cell infiltration analysis indicated a correlation between the AS events and the cancer immune microenvironment. The distribution of AS events in varied EOGC subtypes was uneven. The numbers of AS events related to protein phosphorylation and glycosylation were 82 and 85, respectively, which suggested a high association between AS events and protein modification in EOGC.ConclusionThe study highlighted the vital roles of AS in EOGC, including modulating the specific protein modification and reshaping the cancer immune microenvironment, and yielded new insights into the diagnosis of EOGC as well as cancer treatment.

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hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles

Cited by 91 publications

References 44 publications

NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation

NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Identification of novel alternative splicing events associated with tumorigenesis, protein modification, and immune microenvironment in early-onset gastric cancer

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