Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP by microRNA-149-3p promotes aggressiveness of cancer cells

Bellazzo, Arianna; Minin, Giulio Di; Valentino, Elena; Sicari, Daria; Torre, Denis; Marchionni, Luigi; Serpi, Federica; Stadler, Michael; Taverna, Daniela; Zuccolotto, Gaia; Montagner, Isabella Monia; Rosato, Antonio; Tonon, Federica; Zennaro, Cristina; Agostinis, Chiara; Bulla, Roberta; Mano, Miguel; Sal, Giannino Del; Collavin, Licio

doi:10.1038/s41418-018-0088-5

Cited by 32 publications

(32 citation statements)

References 47 publications

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“…It has been reported that miR-149-3p plays a vital role in various cancers and is induced by some antitumor drugs [36,37,53]. Notably, we found that DCA treatment could induce the binding of p53 to the upstream region (−677 to −477) of miR-149 and that miR-149-3p was upregulated by DCA treatment in a p53-dependent manner.…”

Section: Discussionmentioning

confidence: 48%

Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway

Hou

et al. 2019

Oncogene

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The development of chemoresistance remains a major challenge that accounts for colorectal cancer (CRC) lethality. Dichloroacetate (DCA) was originally used as a metabolic regulator in the treatment of metabolic diseases; here, DCA was assayed to identify the mechanisms underlying the chemoresistance of CRC. We found that DCA markedly enhanced chemosensitivity of CRC cells to fluorouracil (5-FU), and reduced the colony formation due to high levels of apoptosis. Using the microarray assay, we noted that miR-149-3p was involved in the chemoresistance of CRC, which was modulated by wild-type p53 after DCA treatment. In addition, PDK2 was identified as a direct target of miR-149-3p. Mechanistic analyses showed that overexpression of miR-149-3p enhanced 5-FU-induced apoptosis and reduced glucose metabolism, similar to the effects of PDK2 knockdown. In addition, overexpression of PDK2 partially reversed the inhibitory effect of miR-149-3p on glucose metabolism. Finally, both DCA treatment and miR-149-3p overexpression in 5-FU-resistant CRC cells were found to markedly sensitize the chemotherapeutic effect of 5-FU in vivo, and this effect was also validated in a small retrospective cohort of CRC patients. Taken together, we determined that the p53/miR-149-3p/PDK2 signaling pathway can potentially be targeted with DCA treatment to overcome chemoresistant CRC.

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Section: Discussionmentioning

confidence: 48%

Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway

Hou

et al. 2019

Oncogene

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“…For examples, Ru et al demonstrated that miR‐149‐3p was involved in the mechanisms of voltage‐gated K + channels in mediating cell proliferation and apoptosis in human glioma U87‐MG cells , but the specific regulatory molecule mechanism was not clear. In tumor endothelial cells, miR‐149‐3p facilitated the activation of nuclear factor kappa B (NF‐κB) signaling and promoted expression of pro‐inflammatory and pro‐angiogenic factors . Chamorro‐Jorganes et al reported that both miR‐149 and miR‐149* up‐regulated angiogenic responses by regulating fibroblast growth factor 2 but lowered the number of HUVECs .…”

Section: Discussionmentioning

confidence: 99%

Profiling and functional analysis of differentially expressed circular RNAs in high glucose‐induced human umbilical vein endothelial cells

Jin

Wang

et al. 2019

FEBS Open Bio

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Dysfunction of vascular endothelial cells often results in diabetic vascular complications. Circular RNAs (circRNAs) have been implicated in the pathogenesis of various diseases, including diabetes and many vascular diseases. This study aimed to explore the roles of circRNAs in high glucose‐induced human umbilical vein endothelial cells (HUVECs) to elucidate the contributions of circRNAs to diabetic vascular complications. We subjected control and high glucose‐induced HUVECs to RNA sequencing and identified 214 differentially expressed circRNAs (versus control HUVECs, fold change ≥ 2.0, P < 0.05). We then validated seven of these differentially expressed circRNAs by qPCR ( hsa_circ_0008360 , hsa_circ_0005741 , hsa_circ_0003250 , hsa_circ_0045462 , hsa_circ_0064772 , hsa_circ_0007976 , and hsa_circ_0005263 ). A representative circRNA–microRNA (miRNA) network was constructed using the three most up‐regulated circRNAs ( hsa_circ_0008360 , hsa_circ_0000109 , and hsa_circ_0002317 ) and their putative miRNA. Bioinformatic analysis indicated that these circRNAs regulate the expressions of genes involved in vascular endothelial function and angiogenesis through targeting miRNAs. Our work highlights the potential regulatory mechanisms of three crucial circRNAs in diabetes‐associated endothelial dysfunction.

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“…miR-214 overexpression in synovial sarcoma cells did not promote cell growth, migration, nor invasion abilities in vitro, suggesting that it might promote tumor development in a cell non-autonomous manner [34,35]. Gene expression profiling revealed upregulation of inflammatory cytokine genes in synovial sarcoma with miR-214 overexpression.…”

Section: Discussionmentioning

confidence: 93%

Cooperation between SS18-SSX1 and miR-214 in Synovial Sarcoma Development and Progression

Tanaka

Homme

Yamazaki

et al. 2020

Cancers

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SS18-SSX fusion proteins play a central role in synovial sarcoma development, although, the genetic network and mechanisms of synovial sarcomagenesis remain unknown. We established a new ex vivo synovial sarcoma mouse model through retroviral-mediated gene transfer of SS18-SSX1 into mouse embryonic mesenchymal cells followed by subcutaneous transplantation into nude mice. This approach successfully induced subcutaneous tumors in 100% recipients, showing invasive proliferation of short spindle tumor cells with occasional biphasic appearance. Cytokeratin expression was observed in epithelial components in tumors and expression of TLE1 and BCL2 was also shown. Gene expression profiling indicated SWI/SNF pathway modulation by SS18-SSX1 introduction into mesenchymal cells and Tle1 and Atf2 upregulation in tumors. These findings indicate that the model exhibits phenotypes typical of human synovial sarcoma. Retroviral tagging of the tumor identified 15 common retroviral integration sites within the Dnm3 locus as the most frequent in 30 mouse synovial sarcomas. miR-199a2 and miR-214 upregulation within the Dnm3 locus was observed. SS18-SSX1 and miR-214 cointroduction accelerated sarcoma onset, indicating that miR-214 is a cooperative oncomiR in synovial sarcomagenesis. miR-214 functions in a cell non-autonomous manner, promoting cytokine gene expression (e.g., Cxcl15/IL8). Our results emphasize the role of miR-214 in tumor development and disease progression.

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Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP by microRNA-149-3p promotes aggressiveness of cancer cells

Cited by 32 publications

References 47 publications

Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway

Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway

Profiling and functional analysis of differentially expressed circular RNAs in high glucose‐induced human umbilical vein endothelial cells

Cooperation between SS18-SSX1 and miR-214 in Synovial Sarcoma Development and Progression

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