Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disrupted ERK1/2 (MAPK3/MAPK1) MAPK signaling has been associated with several developmental syndromes in humans; however, mutations in ERK1 or ERK2 have not been described. We demonstrate haplo-insufficient ERK2 expression in patients with a novel approximately 1 Mb micro-deletion in distal 22q11.2, a region that includes ERK2. These patients exhibit conotruncal and craniofacial anomalies that arise from perturbation of neural crest development and exhibit defects comparable to the DiGeorge syndrome spectrum. Remarkably, these defects are replicated in mice by conditional inactivation of ERK2 in the developing neural crest. Inactivation of upstream elements of the ERK cascade (B-Raf and C-Raf, MEK1 and MEK2) or a downstream effector, the transcription factor serum response factor resulted in analogous developmental defects. Our findings demonstrate that mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway and suggest that the craniofacial and cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling.
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PMID:Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. 1895 47

Polydatin (PD), a monocrystalline polyphenolic drug mainly found in the roots of Polygonum cuspidatum, has various pharmacological activities. Long non-coding RNAs (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) was found to participate in the suppression of multiple cancers. Here, we proposed to study the effect of PD on myocardial infarction (MI) by inducing DGCR5. CCK-8 assay was performed to detect the viability of H9c2 cells. Flow cytometry was utilized to test apoptosis of H9c2 cells. These results determined the optimal concentration and effect time of hypoxia as well as PD. Si-DGCR5 was transfected into cells and the expression level was determined by qRT-PCR. Western blot was utilized to evaluate the expression of apoptosis-related proteins, Bcl-2, Bax, and cleaved-caspase-3, as well as autophagy-associated proteins including Beclin-1, p62, and LC3-II/LC3-I. As a result, PD efficiently attenuated hypoxia-induced apoptosis and autophagy in H9c2 cells. The expression of DGCR5 was down-regulated by hypoxia and up-regulated by PD. Besides, knocking-down the expression of DGCR5 inhibited the protection of PD in H9c2 cells. In addition, PD up-regulated the accumulation of DGCR5, DGCR5 decreased the expression of Bcl-2 and p62, raised the expression of Bax and cleaved-caspase-3, and the proportion of LC3-II/LC3-I. PD stimulated the PI3K/AKT/mTOR and MEK/ERK signaling pathways via up-regulating the expression of DGCR5. Our data demonstrated that PD reduced cell apoptosis and autophagy induced by hypoxia in cardiomyocytes. Moreover, PD activated PI3K/AKT/mTOR and MEK/ERK signaling pathways by up-regulating the expression of DGCR5.
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PMID:Polydatin protects H9c2 cells from hypoxia-induced injury via up-regulating long non-coding RNA DGCR5. 3275 14

Gallbladder cancer (GBC) is a highly aggressive malignant cancer with poor prognosis. Long noncoding RNA (lncRNA) DiGeorge syndrome critical region gene (DGCR5) has been reported to participate in various types of cancers, but its role in GBC remains largely unknown. This study aimed to explore the functions and mechanisms of DGCR5 in GBC. Here, we found that DGCR5 was upregulated in GBC tissues and cell lines. Through functional experiments, it was demonstrated that silence of DGCR5 significantly suppressed the cell proliferation, migration, invasion, and induced apoptosis and cell cycle arrest in GBC cells. In addition, miR-3619-5p was predicted and further verified as the target of DGCR5. Moreover, miR-3619-5p was observed downregulated in GBC tissues and cell lines, and miR-3619-5p mimics repressed the GBC cell proliferation, migration, invasion and could be rescued by DGCR5 overexpression. Mechanistically, it was found that DGCR5 knockdown and miR-3619-5p mimics inactivated the MEK/ERK1/2 and JNK/p38 MAPK pathways. In addition, rescue experiments indicated that inhibition of MEK/ERK1/2 and JNK/p38 MAPK pathways could reverse the effects of DGCR5 overexpression on cell proliferation, migration and invasion. Finally, xenograft model assay was used to validate that knockdown of DGCR5 suppressed GBC via regulating MEK/ERK1/2 and JNK/p38 MAPK pathways in vivo. Taken together, it was uncovered in our study that DGCR5 exerts an oncogenic role by sponging miR-3619-5p and activating MEK/ERK1/2 and JNK/p38 MAPK pathways in GBC progression.
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PMID:DGCR5 Promotes Gallbladder Cancer by Sponging MiR-3619-5p via MEK/ERK1/2 and JNK/p38 MAPK Pathways. 3274 94