Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer is a common cause of cancer-related deaths worldwide. Squamous cell carcinoma (SCC) is the major histological type of esophageal cancer in developing countries including China, and the prognosis is very poor. Many microRNAs are involved in several important biological and pathologic processes, and promote tumorigenesis. To better understand the prognostic and therapeutic roles of microRNAs in ESCC, we reviewed the diagnosis and prognosis associated oncogenic microRNAs (e.g. miR-21 and miR-17-92 cluster) and tumor suppressor microRNAs (e.g. miR-375, miR-133a and miR-133b), and diagnosis and prognosis associated oncogenic target genes (e.g. PDCD4 and CCND1) and tumor suppressor target genes (e.g. EZH2 and PDK1). We also summarized the prognostic microRNA and target gene pairs (e.g. miR-296 and CCND1, miR214 and EZH2). Taken together, our review highlights the opportunities and challenges for microRNAs in the molecular diagnosis and target therapy of ESCC.
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PMID:MicroRNAs in esophageal squamous cell carcinoma: Potential biomarkers and therapeutic targets. 2826 50

Multiple myeloma remains incurable due to the persistence of a minor population of multiple myeloma cells that exhibit drug resistance, which leads to relapsed and/or refractory multiple myeloma. Elucidating the mechanism underlying drug resistance and developing an effective treatment are critical for clinical management of multiple myeloma. Here we showed that promoting expression of the gene for polycomb-like protein 3 (PHF19) induced multiple myeloma cell growth and multidrug resistance in vitro and in vivo. PHF19 was overexpressed in high-risk and drug-resistant primary cells from patients. High levels of PHF19 were correlated with inferior survival of patients with multiple myeloma, in the Total Therapy 2 cohort and in the Intergroup Francophone du Myeloma (IFM) cohort. Enhancing PHF19 expression levels increased Bcl-xL, Mcl-1, and HIF-1a expression in multiple myeloma cells. PHF19 also bound directly with EZH2 and promoted the phosphorylation of EZH2 through PDK1/AKT signaling. miR-15a is a small noncoding RNA that targeted the 3'UTR of PHF19. We found that downregulation of miR-15a led to high levels of PHF19 in multiple myeloma cells. These findings revealed that PHF19 served a crucial role in multiple myeloma proliferation and drug resistance and suggested that the miR-15a/PHF19/EZH2 pathway made a pivotal contribution to multiple myeloma pathogenesis, offering a promising approach to multiple myeloma treatment. IMPLICATIONS: Our findings identify that PHF19 mediates EZH2 phosphorylation as a mechanism of myeloma cell drug resistance, providing a rationale to explore therapeutic potential of targeting PHF19 in relapsed or refractory patients with multiple myeloma.
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PMID:Polycomb-like Protein 3 Induces Proliferation and Drug Resistance in Multiple Myeloma and Is Regulated by miRNA-15a. 3231 41