Aberrant hnRNP K expression: All roads lead to cancer

Gallardo, Miguel; Hornbaker, Marisa; Zhang, Xiaorui; Hu, Peter; Bueso‐Ramos, Carlos E.; Post, Sean M.

doi:10.1080/15384101.2016.1164372

Cited by 82 publications

(74 citation statements)

References 46 publications

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“…The classification of a specific gene as oncogene or tumor suppressor has been a staple of cancer research. However, this simple classification has become increasingly difficult for some genes [29]. hnRNPK is one of the confused genes.…”

Section: Discussionmentioning

confidence: 99%

“…Its tumor suppressor role has recently been described in acute myeloid leukemia and demonstrated by a haploinsufficient mouse model [22]. In contrast, data from other clinical correlation studies suggest that hnRNPK may be more fittingly described as an oncogene, due to its increased levels in a variety of malignancies [23,[29][30][31][32][33]. hnRNPK itself is a multifunctional protein that might regulate both oncogenic or tumor suppressive pathways through its diverse activates.…”

Section: Discussionmentioning

confidence: 99%

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hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Peng

Liu

et al. 2019

Cancer Cell Int

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Background: The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood.Methods: Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated.Results: The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (− 65 to − 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). Conclusion:These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Peng

Liu

et al. 2019

Cancer Cell Int

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“…Several hnRNP proteins are considered to be proto-oncogenes according to recent studies [119]. Among these members, hnRNP A1, hnRNP K, and PTBP1 (hnRNP I) are involved in apoptosis-related splicing events.…”

Section: Impacts Of Alternative Splicing Events On Apoptosismentioning

confidence: 99%

Differential Impacts of Alternative Splicing Networks on Apoptosis

Lin

Tsao

Lin

2016

IJMS

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Apoptosis functions as a common mechanism to eliminate unnecessary or damaged cells during cell renewal and tissue development in multicellular organisms. More than 200 proteins constitute complex networks involved in apoptotic regulation. Imbalanced expressions of apoptosis-related factors frequently lead to malignant diseases. The biological functions of several apoptotic factors are manipulated through alternative splicing mechanisms which expand gene diversity by generating discrete variants from one messenger RNA precursor. It is widely observed that alternatively-spliced variants encoded from apoptosis-related genes exhibit differential effects on apoptotic regulation. Alternative splicing events are meticulously regulated by the interplay between trans-splicing factors and cis-responsive elements surrounding the regulated exons. The major focus of this review is to highlight recent studies that illustrate the influences of alternative splicing networks on apoptotic regulation which participates in diverse cellular processes and diseases.

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“…Further mechanistic insights, with the aid of chromatin oligonucleotide purification (ChOP) method followed by a mass spectrometry analysis, identified a robust direct interaction between SCAT7 and hnRNPK/YBX1 protein complex. The implication of the latter complex in cell cycle regulation has been established earlier [6,7]; however, SCAT7/hnRNPK/YBX1 axis reinforced a genuine transcriptional activation model through its promoter occupancy over different FGFR members (Figure 1).…”

Section: Commentarymentioning

confidence: 72%