Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence demonstrates that microRNA-22 (miR-22) was deregulated in many types of cancers and was involved in various cellular processes related to carcinogenesis. However, the exact roles and mechanisms of miR-22 remain unknown in human renal cell carcinoma (RCC). Here, the relationship between miR-22 expression pattern and clinicopathological features of patients with EOC were determined by real-time quantitative RT-PCR (qRT-PCR). Furthermore, the role of miR-22 and possible molecular mechanisms in EOC were investigated by several in vitro approaches and in a nude mouse model. Results from qRT-PCR showed that miR-22 was significantly downregulated in RCC samples compared with corresponding non-cancerous tissues, which was significantly associated with tumor stage and lymph node metastasis. Functional study demonstrated that enforced overexpression of miR-22 in renal cancer cells inhibited proliferation, migration and invasion, and induced cell apoptosis in vitro, and suppressed tumor growth in vivo. In addition, SIRT1 was identified as a direct target of miR-22 by a luciferase reporter assay. Overexpression of miR-22 activated p53 and its downstream target p21 and PUMA, and the apoptosis markers cleaved CASP3 and PARP, and inhibited epithelial-mesenchymal transition (EMT). These findings showed that miR-22 functioned as tumor suppressor in RCC and blocked RCC growth and metastasis by directly targeting SIRT1 in RCC, indicating a potential novel therapeutic role in RCC treatment.
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PMID:MicroRNA-22 functions as a tumor suppressor by targeting SIRT1 in renal cell carcinoma. 2649 59

Hereditary epithelial ovarian cancer [EOC] in germline BRCA mutation (gBRCAm) carriers has a distinct clinical behavior characterized by younger age, high- grade serous histology, advanced stage, visceral distribution of disease, high response to platinum and other non-platinum agents and better clinical outcome. Sporadic EOC with homologous recombination deficiency [HDR] but no gBRCAm has the same biological and clinical behavior as EOC in gBRCAm carriers ("BRCAness"phenotype). Biomarkers are in development to enable an accurate definition of molecular features of BRCAness phenotype, and trials are warranted to determine whether such HDR signature will predict sensitivity to PARP inhibitors in sporadic EOC. Moreover, the link between PARP inhibition and angiogenesis suppression, the immunologic properties of EOC in gBRCAm carriers, the HRD induced by PI3K inhibition in EOC cells in vitro strongly support novel clinical trials testing the combination of PARP inhibitors with other biological agents.
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PMID:PARP inhibitors alone and in combination with other biological agents in homologous recombination deficient epithelial ovarian cancer: From the basic research to the clinic. 2847 43