Schip1, a new upstream regulator of Hippo signaling

Chung, Hyunglok; Choi, Kwang‐Wook

doi:10.1080/15384101.2016.1191252

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…Recently, we have shown that Mnat9 is associated with microtubules [ 21 ]. Mer is also known to bind microtubules [ 5 , 31 – 34 ]. Based on the genetic interaction between Mnat9 and Mer, we wondered whether Mnat9 might directly interact with Mer.…”

Section: Resultsmentioning

confidence: 99%

Modulation of Hippo signaling by Mnat9 N-acetyltransferase for normal growth and tumorigenesis in Drosophila

Mok

Choi

2022

Cell Death Dis

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Hippo signaling is a conserved mechanism for controlling organ growth. Increasing evidence suggests that Hippo signaling is modulated by various cellular factors for normal development and tumorigenesis. Hence, identification of these factors is pivotal for understanding the mechanism for the regulation of Hippo signaling. Drosophila Mnat9 is a putative N-acetyltransferase that is required for cell survival by affecting JNK signaling. Here we show that Mnat9 is involved in the negative regulation of Hippo signaling. RNAi knockdown of Mnat9 in the eye disc suppresses the rough eye phenotype of overexpressing Crumbs (Crb), an upstream factor of the Hippo pathway. Conversely, Mnat9 RNAi enhances the eye phenotype caused by overexpressing Expanded (Ex) or Warts (Wts) that acts downstream to Crb. Similar genetic interactions between Mnat9 and Hippo pathway genes are found in the wing. The reduced wing phenotype of Mnat9 RNAi is suppressed by overexpression of Yorkie (Yki), while it is suppressed by knockdown of Hippo upstream factors like Ex, Merlin, or Kibra. Mnat9 co-immunoprecipitates with Mer, implying their function in a protein complex. Furthermore, Mnat9 overexpression together with Hpo knockdown causes tumorous overgrowth in the abdomen. Our data suggest that Mnat9 is required for organ growth and can induce tumorous growth by negatively regulating the Hippo signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Modulation of Hippo signaling by Mnat9 N-acetyltransferase for normal growth and tumorigenesis in Drosophila

Mok

Choi

2022

Cell Death Dis

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“…Zhang et al proposed that IQCJ-Schip1-AS1 could affect the proliferation of colorectal cancer cells through the pathways of cell cycling, DNA replication, and p53 (58). In addition, SCHIP1 is an NF2/ Merlin interacting protein in Drosophila, and its coiled-coil domain interacts with NF2/Merlin to influence the Hippo pathway (52). After the knockdown of SCHIP1, we found that the apoptosis of AML cells increased and the cell growth rate slowed down, which indicated that SCHIP1 may be a malignant promoter of AML.…”

Section: Discussionmentioning

confidence: 99%

A transient receptor potential channel-related model based on machine learning for evaluating tumor microenvironment and immunotherapeutic strategies in acute myeloid leukemia

2022

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BackgroundAcute myeloid leukemia (AML) is an aggressive hematopoietic malignancy. Transient receptor potential (TRP) channels in AML still need to be further explored. A TRP channel-related model based on machine learning was established in this study.MethodsThe data were downloaded from TCGA-LAML and Genome-Tissue Expression (GTEx). TRP-related genes (TRGs) were extracted from previous literature. With the use of Single-Sample Gene Set Enrichment Analysis (ssGSEA), TRP enrichment scores (TESs) were calculated. The limma package was used to identify differentially expressed genes (DEGs), and univariate Cox regression analysis was performed to identify prognostic DEGs. The above prognostic DEGs were analyzed by Random Survival Forest and least absolute shrinkage and selection operator (Lasso) analysis to create the TRP signature. The Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to investigate the efficiency and accuracy of prognostic prediction. Moreover, genomic mutation analysis was based on GISTIC analysis. Based on ESTIMATE, TIMER, MCPcounter, and ssGSEA, the tumor microenvironment and immunological characteristics were expressly evaluated to explore immunotherapeutic strategies. Enrichment analysis for TRP signature was based on the Kyoto Encyclopedia of Genes Genomes (KEGG), Gene Ontology (GO), over-representation analysis (ORA), and Gene Set Enrichment Analysis (GSEA). Genomics of Drug Sensitivity in Cancer (GDSC) and pRRophetic were used to carry out drug sensitivity analysis. Conclusively, SCHIP1 was randomly selected to perform in vitro cyto-functional experiments.ResultsThe worse clinical outcomes of patients with higher TESs were observed. There were 107 differentially expressed TRGs identified. Our data revealed 57 prognostic TRGs. Eight TRGs were obtained to establish the prognostic TRP signature, and the worse clinical outcomes of patients with higher TRP scores were found. The efficiency and accuracy of TRP signature in predicting prognosis were confirmed by ROC curves and five external validation datasets. Our data revealed that the mutation rates of DNMT3A, IDH2, MUC16, and TTN were relatively high. The level of infiltrating immune cell populations, stromal, immune, and ESTIMATE scores increased as the TRP scores increased. Nevertheless, AML patients with lower TRP scores exhibited more tumor purity. The TRP scores were found to be correlated with immunomodulators and immune checkpoints, thus revealing immune characteristics and immunotherapeutic strategies. The IC50 values of six chemotherapeutics were lower in the high TRP score (HTS) group. Finally, it was found that SCHIP1 may be the oncogenic gene.ConclusionThe results of this study will help in understanding the role of TRP and SCHIP1 in the prognosis and development of AML.

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“…Loss of the SCHIP1 protein triggers overproliferation via upregulation of genes targeted by Yorkie (YAP in mammals), indicating that this protein serves as a tumor suppressor regulating the YAP oncogene. [ 26 ] SPINK2 is a member of the family of Kazal-type serine proteinase inhibitors that inhibit trypsin/acrosin; SPINK2 is synthesized principally in the testes and seminal vesicles, promoting fertility. Dysregulation of SPINK2 is closely associated with cancers such as lymphomas; high levels of SPINK2 transcription in patients with primary cutaneous follicular center cell lymphomas are associated with improved prognosis and reduced mortality.…”

Section: Discussionmentioning

confidence: 99%

Identification of the hub genes and pathways involved in acute myeloid leukemia using bioinformatics analysis

Tan

Zheng

et al. 2020

Medicine

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Schip1, a new upstream regulator of Hippo signaling

Cited by 4 publications

References 7 publications

Modulation of Hippo signaling by Mnat9 N-acetyltransferase for normal growth and tumorigenesis in Drosophila

Modulation of Hippo signaling by Mnat9 N-acetyltransferase for normal growth and tumorigenesis in Drosophila

A transient receptor potential channel-related model based on machine learning for evaluating tumor microenvironment and immunotherapeutic strategies in acute myeloid leukemia

Identification of the hub genes and pathways involved in acute myeloid leukemia using bioinformatics analysis

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