miR-125a regulates cell cycle, proliferation, and apoptosis by targeting the ErbB pathway in acute myeloid leukemia

Ufkin, Melanie; Peterson, Sarah; Yang, Xuehui; Driscoll, Heather; Duarte, Christine W.; Sathyanarayana, Pradeep

doi:10.1016/j.leukres.2013.12.021

Cited by 69 publications

(61 citation statements)

References 33 publications

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“…Promoter methylation has been shown to be the mechanism underlying down-regulation of miR-125a in acute myeloid leukemia (32). Our results of the AZA-treated OSCC cells show that the promoter methylation is one of the mechanisms for down-regulation of miR-125a in OSCC (Fig.…”

Section: Discussionmentioning

confidence: 53%

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MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

Tiwari

Swamy

Gopinath

et al. 2014

Journal of Biological Chemistry

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Background: ESRRA is frequently up-regulated in several cancers. However, the mechanism underlying its up-regulation remains elusive. Results: Down-regulation of tumor suppressor miR-125a causes up-regulation of ESRRA in OSCC. Conclusion: Down-regulation of miR-125a is a novel mechanism for up-regulation of ESRRA in OSCC. Significance: Targeting miR-125a via a synthetic mimic adds novelty to OSCC therapeutics.

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Section: Discussionmentioning

confidence: 53%

“…5-Aza-2Јdeoxycytidine Treatment Up-regulates miR-125a-Methylation of the miR-125a promoter has been shown previously (32). To understand the mechanism underlying the down-regulation of miR-125a, we speculated that the promoter of miR-125a is methylated in OSCC cell lines SCC084 and SCC131.…”

Section: Mir-125amentioning

confidence: 88%

MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

Tiwari

Swamy

Gopinath

et al. 2014

Journal of Biological Chemistry

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“…Overexpressed EREG has been linked to dysregulation of mitogen-activated protein kinase signaling via the EGF pathway as well as the ERBB pathway, and this overexpression in the sensitive cells may reflect an underlying drive toward the mitogen-activated protein kinase/ERBB pathways. 54,55 Conversely, in the arginase-resistant cells, overexpression of the heat shock protein HSPA6 was demonstrated, suggesting that this may be a mechanism by which these cells attain resistance, especially in light of the finding that HSP inhibition is cytotoxic to AML. 56 EREG and EGFR signaling, as well as the heat shock protein family, play key roles in solid tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

Mussai

Egan

Higginbotham-Jones

et al. 2015

Blood

139

153

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Key Points• Arginase depletion with BCT-100 pegylated recombinant human arginase is cytotoxic to AML blasts.Acute myeloid leukemia (AML) is one of the most common acute leukemias in adults and children, yet significant numbers of patients relapse and die of disease. In this study, we identify the dependence of AML blasts on arginine for proliferation. We show that AML blasts constitutively express the arginine transporters CAT-1 and CAT-2B, and that the majority of newly diagnosed patients' blasts have deficiencies in the arginine-recycling pathway enzymes argininosuccinate synthase and ornithine transcarbamylase, making them arginine auxotrophic. BCT-100, a pegylated human recombinant arginase, leads to a rapid depletion in extracellular and intracellular arginine concentrations, resulting in arrest of AML blast proliferation and a reduction in AML engraftment in vivo. BCT-100 as a single agent causes significant death of AML blasts from adults and children, and acts synergistically in combination with cytarabine. Using RNA sequencing, 20 further candidate genes which correlated with resistance have been identified. Thus, AML blasts are dependent on arginine for survival and proliferation, as well as depletion of arginine with BCT-100 of clinical value in the treatment of AML. (Blood. 2015;125(15):2386-2396

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“…Inhibition of NRG1/ErbB2 signaling blocks regeneration NRG1 signaling was inhibited with the specific (Nagasawa et al, 2006;Ufkin et al, 2014) ErbB2 inhibitor mubritinib. Submersion in 500 nM mubritinib did not impair wound healing but completely inhibited blastema formation in fully innervated limbs, rendering them outwardly identical to denervated limbs (Fig.…”

Section: Nrg1 Supplementation Rescues Regeneration In Denervated Limbsmentioning

confidence: 99%

Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

et al. 2016

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The Mexican axolotl (Ambystoma mexicanum) is capable of fully regenerating amputated limbs, but denervation of the limb inhibits the formation of the post-injury proliferative mass called the blastema. The molecular basis behind this phenomenon remains poorly understood, but previous studies have suggested that nerves support regeneration via the secretion of essential growthpromoting factors. An essential nerve-derived factor must be found in the blastema, capable of rescuing regeneration in denervated limbs, and its inhibition must prevent regeneration. Here, we show that the neuronally secreted protein Neuregulin-1 (NRG1) fulfills all these criteria in the axolotl. Immunohistochemistry and in situ hybridization of NRG1 and its active receptor ErbB2 revealed that they are expressed in regenerating blastemas but lost upon denervation. NRG1 was localized to the wound epithelium prior to blastema formation and was later strongly expressed in proliferating blastemal cells. Supplementation by implantation of NRG1-soaked beads rescued regeneration to digits in denervated limbs, and pharmacological inhibition of NRG1 signaling reduced cell proliferation, blocked blastema formation and induced aberrant collagen deposition in fully innervated limbs. Taken together, our results show that nerve-dependent NRG1/ErbB2 signaling promotes blastemal proliferation in the regenerating limb and may play an essential role in blastema formation, thus providing insight into the longstanding question of why nerves are required for axolotl limb regeneration.

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miR-125a regulates cell cycle, proliferation, and apoptosis by targeting the ErbB pathway in acute myeloid leukemia

Cited by 69 publications

References 33 publications

MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

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