POU homeodomain protein OCT1 modulates islet 1 expression during cardiac differentiation of P19CL6 cells

Liu, Yinan; Liu, Yanming; Li, Tao; Lü, Huafei; Jia, Zhonghua; Wang, Weiping; Chen, Ping; Ma, Kangtao; Zhou, Chen

doi:10.1007/s00018-010-0544-y

Cited by 14 publications

(16 citation statements)

References 42 publications

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“…The pCDNA3.1-c-MYC, c-MYC-luc, and mutant-c-MYC-luc reporters were constructed previously by our laboratory [30]. The CCNB1-luc, CCNB2-luc, mutant-CCNB1-luc, and mutant-CCNB2-luc reporters were constructed by TransGen Biotech (Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

ISL1, a novel regulator ofCCNB1,CCNB2andc-MYCgenes, promotes gastric cancer cell proliferation and tumor growth

et al. 2016

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Islet-1 (ISL1) belongs to the LIM homeodomain transcription factor family, which is specifically expressed in certain tissue types only. Previously, we reported that ISL1 is aberrantly overexpressed in gastric cancer (GC). However, its role in GC is not clear. Here, we report that ISL1 is aberrantly upregulated not only in human gastric carcinoma tissues but also in some GC cell lines. Upregulated ISL1 expression enhanced xenografted gastric carcinoma development, while ISL1 knockdown inhibited GC growth in nude mice. ISL1 overexpression promoted GC cell proliferation, colony formation, and cell growth in soft agar, and facilitated cell cycle transition in GC cells, demonstrated an increase in the proportion of cells in the G2/M and S phases and a decrease in the proportion of cells in the G1 phase. Furthermore, we provide evidence that ISL1 is a novel regulator of the cyclin B1 (CCNB1), cyclin B2 (CCNB2) and c-myc (c-MYC) genes. ISL1 activated the expression of these genes in GC cells by binding to the conserved binding sites on their promoters or enhancers. The expression levels of the genes were decreased in response to ISL1 knockdown. Therefore, ISL1 may serve as a potential therapeutic target in GC.

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Section: Methodsmentioning

confidence: 99%

ISL1, a novel regulator ofCCNB1,CCNB2andc-MYCgenes, promotes gastric cancer cell proliferation and tumor growth

et al. 2016

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“…However, it is unknown how p-STAT3 and p-c-Jun control ISL-1 expression. Bioinformatic analysis showed that the core transcriptional regulatory region of ISL-1 (-1000 ~ ATG) [30] contains conserved p-STAT3 and p-c-Jun binding sites (Figure 8A). Luciferase assay with ISL-1-luc , a ISL-1 luciferase reporter construct containing the binding site of c-Jun and STAT3, was performed in Ly3 cells treated with IL-6/STATTIC (JAK/STAT signaling activator/inhibitor) or Anisomycin/SP600125 (JNK signaling activator/inhibitor), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The plasmid transfection and luciferase activity detection were performed as described before [30]. ISL-1-luc plasmid was constructed previously by our laboratory [30].…”

Section: Methodsmentioning

confidence: 99%

“…ISL-1-luc plasmid was constructed previously by our laboratory [30]. pCDNA3.1-c-Myc, c-Myc-luc was kindly provided by Prof. Shang YF, Peking University School of Basic Medical Sciences.…”

Section: Methodsmentioning

confidence: 99%

“…RT-PCR and real-time RT-PCR amplifications were performed as descripted before [30] with different primers: ISL-1: F: 5′-CTGCTTTTCAGCAACTGGTCA-3′, R: 5′-TAGGACTGGCTACCATGCTGT-3′; c-Myc: F: 5′-GCCACGTCTCCACACATCAG-3′, R: 5′-TCTTGGCAGCAGGATAGTCCTT-3′; GAPDH: F: 5′-CGACCACTTTGTCAAGCTCA-3′, R: 5′-AGGGGTCTACATGGCAACTG-3′.…”

Section: Methodsmentioning

confidence: 99%

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ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex

et al. 2014

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BackgroundInsulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, is essential for the heart, motor neuron and pancreas development. Recently, ISL-1 has been found in some types of human cancers. However, how ISL-1 exerts the role in tumor development is not clear.Methods and resultsThe expression of ISL-1 was assessed in 211 human lymphoma samples and 23 normal lymph node samples. Immunohistochemistry results demonstrated a markedly higher expression of ISL-1 in 75% of non-Hodgkin lymphoma (NHL) samples compared with that in normal lymph nodes or Hodgkin lymphoma (HL) samples. CCK-8 analysis, cell cycle assay and xenograft model were performed to characterize the association between ISL-1 expression level and biological functions in NHL. The results showed that ISL-1 overexpression obviously promoted NHL cells proliferation, changed the cell cycle distribution in vitro and significantly enhanced xenografted lymphoma development in vivo. Real-time PCR, Western blot, luciferase assay and ChIP assay were used to explore the potential regulatory targets of ISL-1 and the results demonstrated that ISL-1 activated the c-Myc expression in NHL by direct binding to a conserved binding site on the c-Myc enhancer. Further results revealed that ISL-1 could be positively regulated by the c-Jun N-terminal kinase (JNK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Both the JNK and JAK/STAT signaling inhibitors could significantly suppressed the growth of NHL cells through the down-regulation of ISL-1 as demonstrated by CCK-8 and Western blot assays. Bioinformatic analysis and luciferase assay exhibited that ISL-1 was a novel target of p-STAT3 and p-c-jun. ChIP, Co-IP and ChIP-re-IP analysis revealed that ISL-1 could participate with p-STAT3 and p-c-Jun to form a p-STAT3/p-c-Jun/ISL-1 transcriptional complex that binds directly on the ISL-1 promoter, demonstrating a positive feedback regulatory mechanism for ISL-1 expression in NHL.ConclusionsOur results provide the first evidence that ISL-1 is tightly linked to NHL proliferation and development by promoting c-Myc transcription, and its aberrant expression was regulated by p-STAT3/p-c-Jun/ISL-1 complex activation.

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Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4

Guo

Bai

Cheng

et al. 2021

Cancer Communications

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Background Insulin gene enhancer protein 1, (ISL1), a LIM‐homeodomain transcription factor, is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes. However, the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer (GC) is unclear. In this study, we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis. Methods We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real‐time polymerase chain reaction (PCR). Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown. RNA‐sequencing was performed to identify differentially expressed genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) to reveal key signaling pathways likely regulated by ISL1 in GC. Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) and by detecting glucose consumption and lactate production. The expression of glucose transporter 4 (GLUT4) and ISL1 was assessed by Western blotting, immunohistochemistry, and immunofluorescent microscopy. The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4. Results High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients. ISL1 knockdown inhibited cell proliferation both in vitro and in vivo. KEGG analysis and GSEA for RNA‐sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown, which was validated by reduced glucose uptake and lactate production, decreased ECAR, and increased OCR. Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter. Conclusion ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.

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POU homeodomain protein OCT1 modulates islet 1 expression during cardiac differentiation of P19CL6 cells

Cited by 14 publications

References 42 publications

ISL1, a novel regulator ofCCNB1,CCNB2andc-MYCgenes, promotes gastric cancer cell proliferation and tumor growth

ISL1, a novel regulator ofCCNB1,CCNB2andc-MYCgenes, promotes gastric cancer cell proliferation and tumor growth

ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex

Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4

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