This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ribonucleases (RNases) is the collective term used for the group of enzymes that are involved in mRNA degradation. The shortening of the poly (A) tail through deadenylation is the preferred mechanism of degradation of most eukaryotic mRNAs and poly (A)-specific ribonuclease (PARN) is the most important player in deadenylation. Besides its primarily role in mRNA stability, PARN is also involved in several non-conventional functions. It is conceivable that a decreased RNase activity can alter the stability of cancer-associated mRNAs and this alteration may be differential in cells of different origin. Methods: The effects of siRNA-mediated knockdown of PARN on the post-transcriptional expression of 16 oncogenes and 18 tumor suppressor genes in cells derived from different lineages (NCI-H460 and NCI-H522; lung cancer) and (HEK-293; kidney) were investigated. Further, the effects of PARN depletion on proliferation and death of the lung cancer cells were investigated. Results: Quantitative real time PCR analysis revealed an cell-specific alteration in the expression of the target onco and tumor suppressor genes upon PARN depletion, differently, for cells derived from different lineages. The tumor suppressor genes showed a consistent pattern of down regulation upon PARN depletion in all the three cell types tested. In contrast, the expression of oncogenes was not consistent; while some oncogenes showed overexpression in HEK 293 cells, the majority of them were downregulated in the lung cancer cells. Further, PARN depletion did not alter the proliferation of lung cancer cells, which was in contrast to previous reports.
Conclusion:The results of this study reveal that PARN deficiency leads to an altered stability of cancer-associated mRNA, distinctly, in cells of different lineages. Despite previous reports suggesting a potential therapeutic role of PARN in cancer, our results suggest that PARN may not be an important biomarker, particularly in lung cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.