CUL4A expression in pediatric osteosarcoma tissues and its effect on cell growth in osteosarcoma cells

Li, Xin; Xu, Ruijiang; Lv, Hong; Fang, Ke

doi:10.1007/s13277-015-4715-1

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…Lung cancer initiation and progression (transgenic overexpression of Cul4a) [89][90][91] ;Resistant to UV-induced skin carcinogenesis (skin-specific knockout of Cul4a) 55 Overexpressed in multiple myeloma 310 , cholangiocarcinoma 113,114 , gastric cancer [102][103][104] , colorectal cancer 104,[107][108][109] , ovarian cancer 104,112,311 , lung cancer 93,110,111 , breast cancer [104][105][106] , osteosarcoma 312,313 , hepatocellular cancer 117,314 , malignant pleural mesothelioma 315,316 , pituitary adenoma 317 , prostate cancer 318 CUL4B Oncogenic Spontaneous development of liver cancer (transgenic overexpression of Cul4b) 92 Overexpressed in cholangiocarcinoma 120 , pancreatic carcinoma 119 , lung cancer 93 • 118 , colorectal cancer 115,116 , glioma 319 , liver cancer 122 , cervical cancer 121 290,325 HBx Hepatocarcinogenesis in transgenic Hbx mice 129,130 Overexpressed in liver cancer…”

Section: Cul4a Oncogenicmentioning

confidence: 99%

The emerging role for Cullin 4 family of E3 ligases in tumorigenesis

Cheng

Guo

North

et al. 2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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As a member of the Cullin-RING ligase family, Cullin-RING ligase 4 (CRL4) has drawn much attention due to its broad regulatory roles under physiological and pathological conditions, especially in neoplastic events. Based on evidence from knockout and transgenic mouse models, human clinical data, and biochemical interactions, we summarize the distinct roles of the CRL4 E3 ligase complexes in tumorigenesis, which appears to be tissue-and context-dependent. Notably, targeting CRL4 has recently emerged as a noval anti-cancer strategy, including thalidomide and its derivatives that bind to the substrate recognition receptor cereblon (CRBN), and anticancer sulfonamides that target DCAF15 to suppress the neoplastic proliferation of multiple myeloma and colorectal cancers, respectively. To this end, PROTACs have been developed as a group of engineered bi-functional chemical glues that induce the ubiquitinationmediated degradation of substrates via recruiting E3 ligases, such as CRL4 (CRBN) and CRL2 (pVHL). We summarize the recent major advances in the CRL4 research field towards understanding its involvement in tumorigenesis and further discuss its clinical implications. The anti-tumor effects using the PROTAC approach to target the degradation of undruggable targets are also highlighted.

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Section: Cul4a Oncogenicmentioning

confidence: 99%

The emerging role for Cullin 4 family of E3 ligases in tumorigenesis

Cheng

Guo

North

et al. 2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…[ 8 ] For example, CUL4A participates a role in the regulation of osteosarcoma and regulates the cell growth in osteosarcoma. [ 9 ] Besides, knockdown of CUL4A is able to suppress the invasive ability of osteosarcoma cells. [ 10 ] However, few studies have reported the role of CUL4A in osteoclast differentiation.…”

Section: Introductionmentioning

confidence: 99%

CUL4A‐mediated ZEB1/microRNA‐340‐5p/HMGB1 axis promotes the development of osteoporosis

Chen

Zheng

et al. 2023

J Biochem & Molecular Tox

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Understanding the molecular mechanisms underlying osteoclast differentiation provides insights into bone loss and even osteoporosis. The specific mechanistic actions of cullin 4A (CUL4A) in osteoclast differentiation and resultant osteoporosis is poorly explored. We developed a mouse model of osteoporosis using bilateral ovariectomy (OVX) and examined CUL4A expression. It was noted that CUL4A expression was increased in the bone marrow of OVX mice. Overexpression of CUL4A promoted osteoclast differentiation, and knockdown of CUL4A alleviated osteoporosis symptoms of OVX mice. Bioinformatic analyses were applied to identify the downstream target genes of microRNA‐340‐5p (miR‐340‐5p), followed by interaction analysis. The bone marrow macrophages (BMMs) were isolated from femur of OVX mice, which were transfected with different plasmids to alter the expression of CUL4A, Zinc finer E‐box binding homeobox 1 (ZEB1), miR‐340‐5p, and Toll‐like receptor 4 (TLR4). ChIP assay was performed to detect enrichment of ZEB1 promoter by H3K4me3 antibody in BMMs. ZEB1 was overexpressed in the bone marrow of OVX mice. Overexpression of CUL4A mediated H3K4me3 methylation to increase ZEB1 expression, thus promoting osteoclast differentiation. Meanwhile, ZEB1 could inhibit miR‐340‐5p expression and upregulate HMGB1 to induce osteoclast differentiation. Overexpressed ZEB1 activated the TLR4 pathway by regulating the miR‐340‐5p/HMGB1 axis to induce osteoclast differentiation, thus promoting the development of osteoporosis. Overall, E3 ubiquitin ligase CUL4A can upregulate ZEB1 to repress miR‐340‐5p expression, leading to HMGB1 upregulation and the TLR4 pathway activation, which promotes osteoclast differentiation and the development of osteoporosis.

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CUL4A expression is associated with tumor stage and prognosis in nasopharyngeal carcinoma

Jin

Zhu

et al. 2019

Medicine

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Cullin 4A (CUL4A) is a protein of E3 ubiquitin ligase with many cellular processes. CUL4A could regulate cell cycle, development, apoptosis, and genome instability. This study aimed to analyze the expression of CUL4A in nasopharyngeal carcinoma (NPC) tissues and the associations of CUL4A expression with prognostic significance. A total of 115 NPC patients were collected to assess the protein expression of CUL4A by immunohistochemistry, so as to analyze the relationships between CUL4A expression and clinicopathological and prognostic parameters. All patients were followed-up until death or 5 years. The results showed that high expression of CUL4A was significantly associated with larger primary tumor size (P = .026), higher nodal status (P = .013), more distant metastasis (P = .020), and higher TNM stage (P = .005). Kaplan–Meier curves showed that patients with higher CUL4A expression had significantly shorter overall survival (OS) and progression-free survival (PFS) (both P < .001). In multivariate Cox analysis, CUL4A is an independent prognostic factor for OS (P = .016; hazard ratio [HR] = 2.770, 95% CI: 1.208–6.351) and PFS (P = .022; HR = 2.311, 95% CI: 1.126–4.743). In conclusion, high expression of CUL4A was associated with advanced disease status of NPC, and might serve as an independent prognostic factor.

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CUL4A expression in pediatric osteosarcoma tissues and its effect on cell growth in osteosarcoma cells

Cited by 5 publications

References 18 publications

The emerging role for Cullin 4 family of E3 ligases in tumorigenesis

The emerging role for Cullin 4 family of E3 ligases in tumorigenesis

CUL4A‐mediated ZEB1/microRNA‐340‐5p/HMGB1 axis promotes the development of osteoporosis

CUL4A expression is associated with tumor stage and prognosis in nasopharyngeal carcinoma

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