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Article ; Online: The chromatin remodeling factor Arid1a cooperates with Jun/Fos to promote osteoclastogenesis by epigenetically upregulating Siglec15 expression.

Zhang, Yongxing / Sun, Hangxiang / Huang, Fei / Chen, Yang / Ding, Xiying / Zhou, Chenhe / Wu, Yan / Zhang, Qing / Ma, Xiao / Wang, Jun / Yue, Rui / Shen, Li / Sun, Xuxu / Ye, Zhaoming

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2024

Abstract: ... Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion ...

Abstract	Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow-derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell-cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid-binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1093/jbmr/zjae042
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Zs.A 2142: Show issues

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Article ; Online: Andrographolide inhibits Burkitt's lymphoma by binding JUN and CASP3 proteins.

Zeng, Junquan / Zheng, Yongliang / Dong, Si / Ding, Ting / Zhang, Shouhua / Li, Kuangfan / Liu, Haiyun / Fang, Quangang / Yuan, Sheng / Wei, Yujing / Li, Jing / Liu, Tingting

Cancer chemotherapy and pharmacology

2023 Volume 93, Issue 4, Page(s) 381–391

Abstract: ... a increased in the expression of JUN (c-Jun) and CASP3 (Caspase 3) proteins in Burkitt's lymphoma cells ... by inhibiting JUN and CASP3 proteins. ...

Abstract	Background: Burkitt's lymphoma, one of the most common subtypes of pediatric malignant lymphoma, is notorious for its swift onset, aggressive proliferation, pronounced invasiveness, and marked malignancy. The therapeutic landscape for Burkitt's lymphoma currently falls short of providing universally effective and tolerable solutions. Andrographolide, a primary active component of Andrographis paniculata, is renowned for its properties of heat-clearing, detoxification, inflammation reduction, and pain relief. It is predominantly used in treating bacterial and viral infections of the upper respiratory tract, as well as dysentery. Various reports highlight the antitumor effects of andrographolide. Yet, its specific impact and the underlying mechanism of action on Burkitt's lymphoma remain an uncharted area of research. Method: We employed network pharmacology to pinpoint the targets of andrographolide's action on Burkitt's lymphoma and the associated pathways. We then evaluated the impact of andrographolide on Burkitt's lymphoma using both in vitro and in vivo patient-derived xenograft (PDX) models. Concurrently, we confirmed the molecular targets of andrographolide in Burkitt's lymphoma through immunofluorescence assays. Result: Utilizing network pharmacology, we identified 15 relevant targets, 60 interrelationships between these targets, and numerous associated signaling pathways for andrographolide's action on Burkitt's lymphoma. In vitro efficacy tests using High-throughput Drug Sensitivity Testing and in vivo PDX model evaluations revealed that andrographolide effectively curtailed the growth of Burkitt's lymphoma. Moreover, we observed a increased in the expression of JUN (c-Jun) and CASP3 (Caspase 3) proteins in Burkitt's lymphoma cells treated with andrographolide. Conclusion: Andrographolide inhibits the growth of Burkitt's lymphoma by inhibiting JUN and CASP3 proteins.
MeSH term(s)	Humans ; Child ; Burkitt Lymphoma/drug therapy ; Burkitt Lymphoma/metabolism ; Burkitt Lymphoma/pathology ; Caspase 3 ; Diterpenes
Chemical Substances	Caspase 3 (EC 3.4.22.-) ; andrographolide (410105JHGR) ; CASP3 protein, human (EC 3.4.22.-) ; Diterpenes
Language	English
Publishing date	2023-12-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-023-04626-4
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Zs.A 1420: Show issues

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Article ; Online: Correction: Ubiquitous mitochondrial creatine kinase promotes the progression of gastric cancer through a JNK-MAPK/JUN/HK2 axis regulated glycolysis.

Mi, Yushuai / Li, Quanhui / Liu, Bingtian / Wang, Dehai / Liu, Ziping / Wang, Tianshi / Wang, Yuan / Zang, Yifeng / Zhou, Yan / Wen, Yugang / Ding, Yinlu

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association

2024 Volume 27, Issue 3, Page(s) 646–648

Language	English
Publishing date	2024-03-22
Publishing country	Japan
Document type	Published Erratum
ZDB-ID	1463526-4
ISSN	1436-3305 ; 1436-3291
ISSN (online)	1436-3305
ISSN	1436-3291
DOI	10.1007/s10120-024-01490-w
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Article ; Online: Spatio-temporal pattern of c-Jun N-terminal kinase isoforms in the cochleae of C57BL/6J mice with presbycusis.

Ding, Rui / Pan, Yi / Chen, Kaili / Zou, Tianyuan / Zhang, Andi / Guo, Dongye / Ji, Peilin / Fan, Cui / Ye, Bin / Xiang, Mingliang

Hearing research

2023 Volume 434, Page(s) 108784

Abstract: The c-Jun N-terminal kinase (JNK) pathway is a vital component ...

Abstract	The c-Jun N-terminal kinase (JNK) pathway is a vital component of the mitogen-activated protein kinase cascade, which regulates cell death and survival. The present study aimed to explore the Spatio-temporal changes in all JNK isoforms in the cochleae of C57/BL6J mice with age-related hearing loss. Changes in the three isoforms of JNKs in the cochleae of an animal model with presbycusis and the senescent HEI-OC1 cell line were tested by immunohistochemistry staining and western blotting. Our results demonstrated that all three JNK isoforms are distributed in the cochleae, and the expression patterns of JNK1, JNK2, and JNK3 differed in hair cells, spiral ganglion neurons, and stria vascularis, with great significance in the cochleae of adult C57BL/6J mice. The levels of JNK1, JNK2, and JNK3 showed various spatio-temporal changes in the aging mice. In a senescent hair cell model, changes in JNK1, JNK2, and JNK3 expression levels were similar to those observed in the cochleae. Our study is the first to show that JNK3 is highly expressed in the hair cells of C57BL/6J mice and further increases in conjunction with age-related hearing loss, suggesting that it may play a more critical role than previously believed in hair cell loss and spiral ganglion degeneration.
MeSH term(s)	Mice ; Animals ; JNK Mitogen-Activated Protein Kinases/metabolism ; Presbycusis/genetics ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinase 8/genetics ; Mitogen-Activated Protein Kinase 8/metabolism ; Protein Isoforms
Chemical Substances	JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 8 (EC 2.7.11.24) ; Protein Isoforms
Language	English
Publishing date	2023-05-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	282629-x
ISSN	1878-5891 ; 0378-5955
ISSN (online)	1878-5891
ISSN	0378-5955
DOI	10.1016/j.heares.2023.108784
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Zs.A 1467: Show issues

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Article ; Online: Synthesis-accessibility-oriented design of c-Jun N-terminal kinase 1 inhibitor.

Qian, Hewen / Ding, Yuanqing / Deng, Xingyu / Huang, Weiwei / Li, Zhenzhen / Liu, Fengling / Zhang, Jie / Wang, Lihui / Liu, Junping / Yuan, Yaxia / Hou, Shurong / Chen, Xiabin / Ma, Lei

European journal of medicinal chemistry

2023 Volume 256, Page(s) 115442

Abstract: ... and limited treatment options. The c-Jun N-Terminal Kinase 1 (JNK1), a key component of the MAPK ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is a severe and progressive lung disease with poor prognosis and limited treatment options. The c-Jun N-Terminal Kinase 1 (JNK1), a key component of the MAPK pathway, has been implicated in the pathogenesis of IPF and represents a potential therapeutic target. However, the development of JNK1 inhibitors has been slowed, partly due to synthetic complexity in medicinal chemistry modification. Here, we report a synthesis-accessibility-oriented strategy for designing JNK1 inhibitors based on computational prediction of synthetic feasibility and fragment-based molecule generation. This strategy led to the discovery of several potent JNK1 inhibitors, such as compound C6 (IC
MeSH term(s)	Animals ; Mitogen-Activated Protein Kinase 8/metabolism ; Mitogen-Activated Protein Kinase 8/therapeutic use ; Pyrimidines/pharmacology ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/metabolism ; Lung/metabolism ; Fibrosis ; JNK Mitogen-Activated Protein Kinases
Chemical Substances	Mitogen-Activated Protein Kinase 8 (EC 2.7.11.24) ; CC-90001 (JD5ZWE631K) ; Pyrimidines ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2023-05-03
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2023.115442
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Zs.B 784: Show issues

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Article ; Online: Activation of the c-Jun NH

Fung, To Sing / Liu, Ding Xiang

Cell death & disease

2017 Volume 8, Issue 12, Page(s) 3215

Abstract: ... of important cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are known to be activated ... of JNK was not mediated via c-Jun, but involved modulation of the anti-apoptotic protein B-cell lymphoma ...

Abstract	Mitogen-activated protein kinases (MAPKs) are conserved protein kinases that regulate a variety of important cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are known to be activated by various environmental stresses including virus infections. Previously, activation of the JNK pathway has been detected in cells infected with several coronaviruses. However, detailed characterization of the pathway as well as its implication in host-virus interactions has not been fully investigated. Here we report that the JNK pathway was activated in cells infected with the avian coronavirus infectious bronchitis virus (IBV). Of the two known upstream MAPK kinases (MKK), MKK7, but not MKK4, was shown to be responsible for IBV-induced JNK activation. Moreover, knockdown and overexpression experiments demonstrated that JNK served as a pro-apoptotic protein during IBV infection. Interestingly, pro-apoptotic activity of JNK was not mediated via c-Jun, but involved modulation of the anti-apoptotic protein B-cell lymphoma 2 (Bcl2). Taken together, JNK constitutes an important aspect of coronavirus-host interaction, along with other MAPKs.
MeSH term(s)	Animals ; Apoptosis/genetics ; Bronchi/metabolism ; Bronchi/virology ; Cell Line, Tumor ; Cercopithecus aethiops ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Gene Expression Regulation ; Host-Pathogen Interactions ; Humans ; Infectious bronchitis virus/pathogenicity ; Infectious bronchitis virus/physiology ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases/genetics ; JNK Mitogen-Activated Protein Kinases/metabolism ; MAP Kinase Kinase 4/genetics ; MAP Kinase Kinase 4/metabolism ; MAP Kinase Kinase 7/genetics ; MAP Kinase Kinase 7/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-jun/genetics ; Proto-Oncogene Proteins c-jun/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Signal Transduction ; Vero Cells
Chemical Substances	BCL2 protein, human ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-jun ; RNA, Small Interfering ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; MAP Kinase Kinase 4 (EC 2.7.12.2) ; MAP Kinase Kinase 7 (EC 2.7.12.2) ; MAP2K4 protein, human (EC 2.7.12.2) ; MAP2K7 protein, human (EC 2.7.12.2)
Keywords	covid19
Language	English
Publishing date	2017-12-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-017-0053-0
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Article ; Online: CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway.

Wang, Xiaojuan / Liu, Yumin / Ding, Yawen / Feng, Gang

Scientific reports

2022 Volume 12, Issue 1, Page(s) 16899

Abstract: ... promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated ... migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating ...

Abstract	CAMSAP2 has been reported to act as an oncogene in hepatocellular carcinoma. However, the expression CAMSAP2 and its potential roles in colorectal cancer remain unclear. In this study, qRT-PCR and immunoblotting analysis were used to detect the mRNA and protein levels of CAMSAP2 in colorectal cancer tissues and cell lines. Wound-healing, transwell migration and invasion assay were performed to determine whether CAMSAP2 promotes the capabilities of migration and invasion of colorectal cancer cells. The results showed that CAMSAP2 was highly elevated in colorectal cancer tissues and cell lines. Moreover, the high CAMSAP2 expression was positively correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and the poor prognosis of colorectal cancer. Additionally, ectopic expression of CAMSAP2 in colorectal cancer cells promoted the migration and invasion in vitro and enhanced the lung metastasis in nude mice. Conversely, silencing CAMSAP2 resulted in an opposite phenomenon. By gain- and loss-of function experiments, we demonstrated that MMP-1 was a substantial downstream target of CAMSAP2, and it played a crucial role in regulating the migration and invasion induced by CAMSAP2 in colorectal cancer cells. Mechanistically, CAMSAP2 promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated the transcription activity of MMP-1. Taken together, our findings demonstrated that CAMSAP2 promoted colorectal cancer cell migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating CAMSAP2 is a promising therapeutic target for the treatment of metastatic colorectal cancer patients.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation ; Colorectal Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; JNK Mitogen-Activated Protein Kinases/metabolism ; Liver Neoplasms/pathology ; MAP Kinase Signaling System ; Matrix Metalloproteinase 1/genetics ; Matrix Metalloproteinase 1/metabolism ; Mice ; Mice, Nude ; Microtubule-Associated Proteins/metabolism ; Neoplasm Invasiveness/genetics ; RNA, Messenger/metabolism
Chemical Substances	Camsap2 protein, mouse ; Microtubule-Associated Proteins ; RNA, Messenger ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Matrix Metalloproteinase 1 (EC 3.4.24.7)
Language	English
Publishing date	2022-10-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-21345-7
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Article ; Online: Ubiquitous mitochondrial creatine kinase promotes the progression of gastric cancer through a JNK-MAPK/JUN/HK2 axis regulated glycolysis.

Mi, Yushuai / Li, Quanhui / Liu, Bingtian / Wang, Dehai / Liu, Ziping / Wang, Tianshi / Wang, Yuan / Zang, Yifeng / Zhou, Yan / Wen, Yugang / Ding, Yinlu

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association

2022 Volume 26, Issue 1, Page(s) 69–81

Abstract: ... enhanced GC progression in a HK2-dependent glycolysis via acting the JNK-MAPK/JUN signaling pathway ...

Abstract	Background: Ubiquitous mitochondrial creatine kinase (uMtCK) transfers high-energy phosphates from mitochondrially generated ATP to creatine to generate phosphocreatine. uMtCK overexpression has been reported in several malignant tumors, however, the clinical significance and impact of uMtCK in gastric cancer (GC) has not been comprehensively studied. Methods: We first examined uMtCK expression in GC by quantitative real-time PCR and western blot assays. Then the clinicopathological significance of aberrant uMtCK expression was determined by immunohistochemical staining in a GC tissue microarray. Kaplan-Meier analysis was used for survival analysis. The biological functions of uMtCK in GC cells were explored by wound-healing, transwell assays and glucose metabolism assays in vitro as well as a liver metastasis model by spleen injection in nude mice in vivo. Results: We verified that the expression of uMtCK was substantially elevated in GC tissues, significantly associating with a poorer prognosis in GC patients, especially for those with advanced stage. In univariate and multivariate analyses, uMtCK expression emerged as an independent prognostic factor for both disease-free survival and overall survival. Functionally, we demonstrated that uMtCK promoted glycolysis in GC cells and facilitated their migration, invasion and liver metastasis in vitro and in vivo. Mechanistically, uMtCK enhanced GC progression in a HK2-dependent glycolysis via acting the JNK-MAPK/JUN signaling pathway. Conclusions: uMtCK could serve as a novel independent prognostic biomarker as well as potential therapeutic target for GC patients, particularly for GC patients with an advanced UICC stage and tumor recurrence.
MeSH term(s)	Mice ; Animals ; Humans ; Stomach Neoplasms/pathology ; Creatine Kinase, Mitochondrial Form/metabolism ; Mice, Nude ; Liver Neoplasms ; Glycolysis ; Cell Proliferation ; Prognosis ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor
Chemical Substances	Creatine Kinase, Mitochondrial Form (EC 2.7.3.2)
Language	English
Publishing date	2022-09-16
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1463526-4
ISSN	1436-3305 ; 1436-3291
ISSN (online)	1436-3305
ISSN	1436-3291
DOI	10.1007/s10120-022-01340-7
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Zs.A 5290: Show issues

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Article ; Online: Map4k4 is up-regulated and modulates granulosa cell injury and oxidative stress in polycystic ovary syndrome via activating JNK/c-JUN pathway: An experimental study.

Ding, Lifeng / Jiang, Lili / Xing, Ze / Dai, Huixu / Wei, Jingzan

International immunopharmacology

2023 Volume 124, Issue Pt A, Page(s) 110841

Abstract: ... attenuated the PCOS-related GC oxidative stress and apoptosis. Mechanically, Map4k4 activated the JNK/c-JUN ... by activating JNK/c-JUN pathway in PCOS. The Map4k4/JNK/c-JUN mechanism may provide a new idea on the treatment ...

Abstract	The regulatory mechanism on granulosa cells (GCs) oxidative injury is becoming increasingly important in polycystic ovary syndrome (PCOS) studies. Serine/threonine kinase mitogen-activated protein 4 kinase 4 (Map4k4) is linked with oxidative injury and possibly associated with premature ovarian failure and ovarian dysgenesis. Herein, we investigated the function and mechanism of Map4k4 in a PCOS rat model. A microarray from GEO database identified Map4k4 was up-regulated in the ovarian of PCOS rats, and functional enrichments suggested that oxidative stress-associated changes are involved. We verified the raised Map4k4 expression in an established PCOS rat model and also in the isolated PCOS-GCs, which were consistent with the microarray data. Map4k4 knockdown in vivo contributed to regular estrous cycle, restrained steroid concentrations and ovarian injury in PCOS rats. Both Map4k4 silencing in vivo and in vitro attenuated the PCOS-related GC oxidative stress and apoptosis. Mechanically, Map4k4 activated the JNK/c-JUN signaling pathway. Importantly, a JNK agonist restored the suppressive effects of Map4k4 silencing on PCOS-induced granulosa cell injury and oxidative stress. Besides, Map4k4 may be a target gene of miR-185-5p. In conclusion, Map4k4, a potential target of miR-185-5p, is up-regulated and induces ovarian GC oxidative injury by activating JNK/c-JUN pathway in PCOS. The Map4k4/JNK/c-JUN mechanism may provide a new idea on the treatment of PCOS.
Language	English
Publishing date	2023-08-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.110841
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Article ; Online: The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer.

Liu, Yanqing / Chen, Xiaorui / Cheng, Rongjie / Yang, Fei / Yu, Mengchao / Wang, Chen / Cui, Shufang / Hong, Yeting / Liang, Hongwei / Liu, Minghui / Zhao, Chihao / Ding, Meng / Sun, Wu / Liu, Zhijian / Sun, Feng / Zhang, Chenyu / Zhou, Zhen / Jiang, Xiaohong / Chen, Xi

Molecular cancer

2018 Volume 17, Issue 1, Page(s) 11

Abstract: ... transcriptional factors that could affect miR-22. Luciferase assay was used to explore the validity of putative Jun ... xenografted tumour growth in vivo. Furthermore, we found that the onco-transcription factor Jun could inhibit ... the transcription of miR-22.: Conclusions: Our findings highlight the critical roles of the Jun/miR-22/HuR ...

Abstract	Background: Colorectal cancer (CRC) is a severe health problem worldwide. Clarifying the mechanisms for the deregulation of oncogenes and tumour suppressors in CRC is vital for its diagnosis, treatment, prognosis and prevention. Hu antigen R (HuR), which is highly upregulated in CRC, functions as a pivotal oncogene to promote CRC progression. However, the underlying cause of its dysregulation is poorly understood. Methods: In CRC tissue sample pairs, HuR protein levels were measured by Western blot and immunohistochemical (IHC) staining, respectively. HuR mRNA levels were also monitored by qRT-PCR. Combining meta-analysis and microRNA (miRNA) target prediction software, we predicted miRNAs that targeted HuR. Pull-down assay, Western blot and luciferase assay were utilized to demonstrate the direct binding of miR-22 on HuR's 3'-UTR. The biological effects of HuR and miR-22 were investigated both in vitro by CCK-8, EdU and Transwell assays and in vivo by a xenograft mice model. JASPAR and SABiosciences were used to predict transcriptional factors that could affect miR-22. Luciferase assay was used to explore the validity of putative Jun binding sites for miR-22 regulation. ChIP assay was performed to test the Jun's occupancy on the C17orf91 promoter. Results: We observed a significant upregulation of HuR in CRC tissue pairs and confirmed the oncogenic function of HuR both in vitro and in vivo. We found that an important tumour-suppressive miRNA, miR-22, was significantly downregulated in CRC tissues and inversely correlated with HuR in both CRC tissues and CRC cell lines. We demonstrated that miR-22 directly bound to the 3'-UTR of HuR and led to inhibition of HuR protein, which repressed CRC proliferation and migration in vitro and decelerated CRC xenografted tumour growth in vivo. Furthermore, we found that the onco-transcription factor Jun could inhibit the transcription of miR-22. Conclusions: Our findings highlight the critical roles of the Jun/miR-22/HuR regulatory axis in CRC progression and may provide attractive potential targets for CRC prevention and treatment.
MeSH term(s)	3' Untranslated Regions ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics ; Colorectal Neoplasms/genetics ; Databases, Genetic ; Disease Models, Animal ; ELAV-Like Protein 1/genetics ; Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Genes, jun ; Heterografts ; Humans ; Mice ; MicroRNAs/genetics ; Models, Biological ; Oncogenes ; RNA Interference ; Transcription, Genetic
Chemical Substances	3' Untranslated Regions ; ELAV-Like Protein 1 ; ELAVL1 protein, human ; MIRN22 microRNA, human ; MicroRNAs
Language	English
Publishing date	2018-01-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1476-4598
ISSN (online)	1476-4598
DOI	10.1186/s12943-017-0751-3
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