MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BDCAF13 E3 Ligase in Osteosarcoma Cells

Chen, Zhi; Zhang, Wei; Jiang, Kaibiao; Chen, Bin; Wang, Kun; Lao, Li; Hou, Canglong; Wang, Fei; Zhang, Caiguo; Shen, Hongxing

doi:10.1016/j.omtn.2017.12.010

Cited by 50 publications

(81 citation statements)

References 55 publications

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“…34 Moreover, recent studies have revealed that protein ubiquitination and protein binding in osteosarcoma provide a new avenue for osteosarcoma therapy. [35][36][37][38][39][40] In other words, all these theories are in agreement with our results. GO enrichment analysis revealed that changes in the hub genes were mainly enriched in nucleolus, protein ubiquitination, and protein binding, while enriched in RNA transport and the spliceosome in the KEGG pathway.…”

Section: Discussionsupporting

confidence: 93%

Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma

Jin

Guo

et al. 2019

J of Cellular Biochemistry

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Osteosarcoma is one of the most malignant tumors in adolescents with severe outcomes while fluoride is one of the most abundant elements in the environment. Epidemiological evidence has elucidated the relationship between fluoride and osteosarcoma, but the molecular mechanisms are extremely complicated. Microarray profiles were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in the progression of fluoride‐affected osteosarcoma. The functional enrichment analysis was performed, a protein‐protein interaction network, a microRNA‐messenger RNA (mRNA) and a transcription factors‐mRNA regulatory network were constructed and performed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. A total of 171 DEGs were identified. The functions and pathways of the DEGs were enriched in nucleolus, protein ubiquitination, protein binding, RNA transport, and the spliceosome. Eighteen hub genes were identified and functional analysis revealed that these genes are mainly enriched in protein binding, nucleoplasm, and ribosomal RNA processing. Survival analysis showed that the hub genes may be involved in the invasion or recurrence of osteosarcoma. In conclusion, the DEGs and hub genes with their regulatory elements identified in this study will help us understand the molecular mechanisms underlying fluoride‐affected osteosarcoma and provide candidate targets for future research.

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Section: Discussionsupporting

confidence: 93%

Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma

Jin

Guo

et al. 2019

J of Cellular Biochemistry

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“…Cullins can form E3 ligases and participate in the tumorigenesis of many cancer types . To test whether cullin family members are involved in the tumorigenesis of CAC, we isolated RNAs from cancerous tissues and their adjacent non‐tumour tissues in 48 CAC patients and examined the mRNA levels of cullins.…”

Section: Resultsmentioning

confidence: 99%

“…The human genome encodes two E1s, ∼40 E2s and more than 600 E3s . Of these E3 ligases, Cullin‐RING ligases (CRLs), the largest subfamily that is conservatively formed by cullins (CUL1, ‐2, ‐3, ‐4A, ‐4B, ‐5 and ‐7), RBX1, DDB1 and DDB1‐ and CUL4‐associated factors (DCAFs), ubiquitinate ∼20% of cellular proteins . Dysregulation of cullin proteins, especially CUL4A and CUL4B, in different cancer types including breast cancer , hepatocellular carcinoma and osteosarcoma is widely known.…”

Section: Introductionmentioning

confidence: 99%

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Inflammation‐dependent overexpression of c‐Myc enhances CRL4^DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer

Liu

et al. 2019

The Journal of Pathology

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Inflammation is well known as an important driver of the initiation of colitis-associated cancer (CAC). Some cytokines, such as IL-6 and TNF- can activate expression of the oncogene c-Myc (MYC) and regulate its downstream effects. Cullin-RING E3 Ligases (CRLs) are emerging as master regulators controlling tumorigenesis.Here, we demonstrate that two cullin genes, CUL4A and CUL4B, but not other members, are specifically overexpressed in CAC tumour samples and positively correlate with levels of the proinflammatory cytokines IL-1 and IL-6. In vitro experiments revealed that the transcription factor c-Myc can specifically activate the expression of CUL4A and CUL4B by binding to a conserved site (CACGTG) located in their promoters. Additionally, we found that both CUL4A and CUL4B can form an E3 complex with DNA damage-binding protein 1 (DDB1) and DDB1-CUL4-associated factor 4 (DCAF4). In vitro and in vivo ubiquitination analyses indicate that CRL4 DCAF4 E3 ligase specifically directs degradation of ST7 (suppression of tumorigenicity 7). Overexpression of c-Myc in human colon epithelial cells resulted in the accumulation of CUL4A, CUL4B and DCAF4, but degradation of ST7. In contrast, knockdown of c-Myc, CUL4A or CUL4B in the colon adenocarcinoma cell line HT29 caused accumulation of ST7 and inhibition of cell proliferation, colony formation ability and in vivo tumour growth. Collectively, our results provide in vitro and in vivo evidence that c-Myc regulates CRL4 DCAF4 E3 ligase activity to mediate ubiquitination of ST7, whose presence is physiologically essential for CAC tumorigenesis.No conflicts of interest were declared. ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) [16,17]. The human genome encodes two E1s, ∼40 E2s and more than 600 E3s [18,19]. Of these E3 ligases, Cullin-RING

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“…Our previous work revealed that miR-323a-3p, miR-433 and miR-409 transcribed from this cluster acted as tumor suppressors [16][17][18]. miR-300, belonging to the DLK1-DIO3 miRNA cluster, was previously reported to be associated with human osteosarcoma, pancreatic cancer, non-small cell lung cancer, glioblastoma, and oral squamous cell carcinoma [20][21][22][23][24]. However, to the best of our knowledge, the role miR-300 in BCa and its mechanism remains unresolved.…”

Section: Introductionmentioning

confidence: 99%

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway

Yan

Ying

et al. 2018

Cell Cycle

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Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation. Reinforced expression of miR-300 significantly suppressed the migration of BCa cells. We carried out a search of online databases to predict potential targets of miR-300. Further studies determined that miR-300 directly targeted SP1 and suppressed its expression by specifically binding to its 3ʹ-untranslated region. Meanwhile, downregulated MMP9 may be the final effector of BCa cell mobility. Small interference RNAs silencing SP1 phenocopied the effects of miR-300 overexpression, while restoration of SP1 expression partially rescued the inhibition of metastasis induced by miR-300 overexpression in BCa cells. In conclusion, we unveiled a miR-300/SP1/MMP9 pathway in BCa. These findings demonstrate that miR-300 is a promising tumor suppressor in BCa. ARTICLE HISTORY

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MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BDCAF13 E3 Ligase in Osteosarcoma Cells

Cited by 50 publications

References 55 publications

Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma

Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma

Inflammation‐dependent overexpression of c‐Myc enhances CRL4^DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway

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MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BDCAF13 E3 Ligase in Osteosarcoma Cells

Cited by 50 publications

References 55 publications

Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma

Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma

Inflammation‐dependent overexpression of c‐Myc enhances CRL4DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway

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Inflammation‐dependent overexpression of c‐Myc enhances CRL4^DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer