HIPK1 drives p53 activation to limit colorectal cancer cell growth

Rey, Christophe; Soubeyran, Isabelle; Mahouche, Isabelle; Pédeboscq, S.; Bessede, Alban; Ichas, François; Giorgi, Francesca De; Lartigue, Lydia

doi:10.4161/cc.24927

Cited by 31 publications

(32 citation statements)

References 50 publications

(94 reference statements)

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“…Interestingly, a large proportion of these genes (81%, 94/116) were repressed by MYCN. Moreover, among these enriched targets of MYCN-regulated miRNAs, some of them, such as KLF6 [70], RASSF8 [71], TGFBR3 [72], ARNTL [73], NDRG4 [74], PHTF1 [75], HIPK1 [76], PTGER4 [77], HECA [78], and EOMES [79], are known as tumor suppressor genes and are suggested as therapeutic targets in other cancer types. This implies that MYCN and MYCN-regulated miRNAs act together to down-regulate tumor suppressor genes.…”

Section: Resultsmentioning

confidence: 99%

Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data

Hsu

Chang

et al. 2016

Oncotarget

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MYCN, an oncogenic transcription factor of the Myc family, is a major driver of neuroblastoma tumorigenesis. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets for neuroblastoma therapy. Here we perform ChIP-sequencing and small RNA-sequencing of neuroblastoma cells to determine the MYCN-binding sites and MYCN-associated microRNAs, and integrate various types of genomic data to construct MYCN regulatory networks. The overall analysis indicated that MYCN-regulated genes were involved in a wide range of biological processes and could be used as signatures to identify poor-prognosis MYCN-non-amplified patients. Analysis of the MYCN binding sites showed that MYCN principally served as an activator. Using a computational approach, we identified 32 MYCN co-regulators, and some of these findings are supported by previous studies. Moreover, we investigated the interplay between MYCN transcriptional and microRNA post-transcriptional regulations and identified several microRNAs, such as miR-124-3p and miR-93-5p, which may significantly contribute to neuroblastoma pathogenesis. We also found MYCN and its regulated microRNAs acted together to repress the tumor suppressor genes. This work provides a comprehensive view of MYCN regulations for exploring therapeutic targets in neuroblastoma, as well as insights into the mechanism of neuroblastoma tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data

Hsu

Chang

et al. 2016

Oncotarget

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“…In addition, HIPK1 modulates different stress pathways implicating them in several types of cancer . HIPK1 has been linked to apoptosis pathways through p53 and apoptosis signal‐research regulating kinase1 (ASK1), to growth pathways through mediation of death‐domain associated protein 6 (Daxx) and also has been found to be involved with the WNT/β‐catenin signaling pathway regulating transcription, cell fate and cell proliferation …”

Section: Discussionmentioning

confidence: 99%

Identifying HIPK1 as Target of miR‐22‐3p Enhancing Recombinant Protein Production From HEK 293 Cell by Using Microarray and HTP siRNA Screen

Inwood

Buehler

Betenbaugh

et al. 2017

Biotechnology Journal

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Protein expression from human embryonic kidney cells (HEK 293) is an important tool for structural and clinical studies. It is previously shown that microRNAs (small, noncoding RNAs) are effective means for improved protein expression from these cells, and by conducting a high-throughput screening of the human microRNA library, several microRNAs are identified as potential candidates for improving expression. From these, miR-22-3p is chosen for further study since it increased the expression of luciferase, two membrane proteins and a secreted fusion protein with minimal effect on the cells' growth and viability. Since each microRNA can interact with several gene targets, it is of interest to identify the repressed genes for understanding and exploring the improved expression mechanism for further implementation. Here, the authors describe a novel approach for identification of the target genes by integrating the differential gene expression analysis with information obtained from our previously conducted high-throughput siRNA screening. The identified genes were validated as being involved in improving luciferase expression by using siRNA and qRT-PCR. Repressing the target gene, HIPK1, is found to increase luciferase and GPC3 expression 3.3- and 2.2-fold, respectively.

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“…HIPK1 directly phophorylates TP53 on its serine-15. Serine 15 phosphorylation induces a rise in CDKN1A (p21, 6p21.2) expression and cell cycle arrest (Rey et al, 2013). HIPK1 phosphorylates DAXX (6p21.32), a protein which interacts with PML (15q24.1), the organizer of nuclear bodies (Ecsedy et al, 2003), and which relocalizes from the nucleus to the cytoplasm in response to stress.…”

Section: Hipk1mentioning

confidence: 99%

“…The highest peak of HIPK1 expression occurred at early stages and decreased in latter stages. HIPK1 appeared to be induced as a defense mechanism to fight against intern deregulations and stressful conditions, rather than produced by the cancer cells as an indispensable factor for tumor evolution (Rey et al, 2013). HIPK1 is expressed only in invasive breast cancer cells with three different subcellular localization, associated with different tumor histopathologic characteristics (Park et al, 2012).…”

Section: Hipk1mentioning

confidence: 99%