Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human ribonuclease inhibitor (RI) is a cytoplasmic acidic protein. RI is constructed almost entirely of leucine rich repeats, which might be involved in unknown biological effects except inhibiting RNase A and angiogenin activities. We previously reported that up-regulating RI inhibited the growth and metastasis of melanoma cells. Epithelial-mesenchymal transition (EMT) is a critical event of cancer cells that triggers invasion and metastasis. However, the role of RI in the EMT process remains unknown. Here we hypothesize that RI might inhibit melanoma invasion and metastasis by regulating EMT. We found that over-expression of RI induced up-regulation of E-cadherin, accompanied with decreased expressions of proteins associated with EMT such as N-cadherin, Snail, Slug, Vimentin and Twist both in vitro and in vivo. Furthermore, RI restrained matrix metalloproteinase MMP-2 and MMP-9 secretions in B16 and B16-F10 melanoma cells. In addition, we also found that up-regulation of RI inhibited cell proliferation, migration and invasion as well as changed cell morphology, adhesion and rearranged cytoskeleton in vitro. Finally, the effects of RI on phenotype and invasiveness translated into suppressing metastasis by the experimental metastasis models of melanoma with lighter lung weight, a fewer metastasis nodules and a lower incidence rate, with respect to the control groups. Taken together, our data highlight, for the first time, that RI plays a novel role in inhibiting development and progression of murine melanoma cells through regulating EMT. These results suggest that RI could be a therapeutic target protein for melanoma and may be of biological importance.
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PMID:Up-regulating ribonuclease inhibitor inhibited epithelial-to-mesenchymal transition and metastasis in murine melanoma cells. 2246 10

Accumulating evidences implicate that ribonuclease inhibitor (RI) plays a suppressing role in cancer development. However, the mechanisms underlying antitumor of RI remain largely unknown. Epithelial-mesenchymal transition (EMT) is regarded as a key event in tumor progression. The reports have demonstrated that EMT was implicated in metastasis of bladder cancer. Therefore, we suppose that RI might involve regulating EMT of bladder cancer. Here bladder cancer T24 cells were transfected with pGensil-1-siRNA-RI vectors. HE staining, living cell observation, Phalloidine-FITC staining of microfilament, cell adhesion, scratch migration, and Matrigel invasion were examined respectively. RI expression and colocalization with ILK were detected using confocal microscope. Proteins associated with EMT were determined with Western blotting and immunohistochemistry in vivo and in vitro. Effects of RI expression on tumor growth, metastasis and EMT related proteins in BALB/C nude mouse and clinical human bladder cancer specimens were valued with histological, immunohistochemical and immunofluorescent examination respectively. We demonstrated that down-regulating RI increased cell proliferation, migration and invasion, changed cell morphology and adhesion, and rearranged cytoskeleton by inducing EMT and ILK signaling pathway in bladder cancer cells. In addition, we showed that down-regulating RI promoted tumorigenesis and metastasis of bladder cancer in vivo. Finally, we found that bladder cancer with invasive capability had higher Vimentin, Snail, Slug and Twist as well as lower E-cadherin and RI expression in clinical human specimens. Our results suggest that RI could play a novel role in inhibiting metastasis of bladder through regulating EMT and ILK signaling pathway.
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PMID:Down-regulating ribonuclease inhibitor enhances metastasis of bladder cancer cells through regulating epithelial-mesenchymal transition and ILK signaling pathway. 2476 14