PubMed · 8107769
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A Sidow. 1994-01-06. Parsimony or statistics?. https://doi.org/10.1038/367026a0
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Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelial-mesenchymal transition (EMT)-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 3' untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer.
Through exhaustive two-hybrid screens using a budding yeast genomic library, and starting with the splicing factor and DEAH-box RNA helicase Prp22p as bait, we identified yeast Prp45p and Prp46p. We show that as well as interacting in two-hybrid screens, Prp45p and Prp46p interact with each other in vitro. We demonstrate that Prp45p and Prp46p are spliceosome associated throughout the splicing process and both are essential for pre-mRNA splicing. Under nonsplicing conditions they also associate in coprecipitation assays with low levels of the U2, U5, and U6 snRNAs that may indicate their presence in endogenous activated spliceosomes or in a postsplicing snRNP complex.
Plasmid libraries containing partially randomized cleavage sites for the eukaryotic homing endonucleases I-PpoI and I-CreI were constructed, and sites that could be cleaved by I-PpoI or I-CreI were selectively recovered by successive cycles of cleavage and gel separation followed by religation and growth in Escherichia coli. Twenty-one different I-PpoI-sensitive homing sites, including the native homing site, were isolated. These sites were identical at four nucleotide positions within the 15 bp homing site, had a restricted pattern of base substitutions at the remaining 11 positions and displayed a preference for purines flanking the top strand of the homing site sequence. Twenty-one different I-CreI-sensitive homing sites, including the native site, were isolated. Ten nucleotide positions were identical in homing site variants that were I-CreI-sensitive and required the addition of SDS for efficient cleavage product release. Four of these ten positions were identical in homing sites that did not require SDS for product release. There was a preference for pyrimidines flanking the top strand of the homing site sequence. Three of the 24 I-CreI homing site nucleotide positions apparently lacked informational content, i. e. were permissive of cleavage when occupied by any nucleotide. These results suggest that I-PpoI and I-CreI make a large number of DNA-protein contacts across their homing site sequences, and that different subsets of these contacts may be sufficient to maintain a high degree of sequence-specific homing site recognition and cleavage. The sequential enrichment protocol we used should be useful for defining the sequence degeneracy and informational content of other homing endonuclease target sites.