The association of elevated 2',5'-oligoadenylate-dependent RNase L with lung cancer correlated with deficient enzymatic activity and decreased capacity of RNase L dimerization.

Abstract

RNase L mediates critical cellular functions including antiviral, proapoptotic, antiproliferative and tumor suppressive activities. In this study, the expression and function of RNase L in lung cancer cells were examined. Interestingly we have found that the expression of RNase L in lung cancer cells was 3- and 9-fold higher in its mRNA and protein levels, but a significant decrease of its enzymatic activity when compared to that in corresponding normal lung cells. Further investigation revealed that 2-5A-induced dimerization of the RNase L protein, a necessary prerequisite for activation of RNase L, was inhibited, as a result of that RLI, a specific inhibitor of RNase L, was remarkably up-regulated in the cancer cells. Our findings provide new insight into how cancer cells escape normal growth-regulating mechanisms to form a tumor and the information may be useful for the design of novel strategies for treating lung cancer through regulating RNase L activity.

• Authors: Huijing Yin, Aimin Zhou, Yalei Dai
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 78 Issue 1 Pg. 30-8 (Oct 2012) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 22925698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Adenine Nucleotides
• Oligoribonucleotides
• Protein Synthesis Inhibitors
• 2',5'-oligoadenylate
• Endoribonucleases
• 2-5A-dependent ribonuclease

Topics

• Adenine Nucleotides (pharmacology)
• Cell Line, Tumor
• Endoribonucleases (chemistry, genetics, metabolism)
• Enzyme Activation (drug effects, genetics)
• Humans
• Lung Neoplasms (enzymology, genetics)
• Oligoribonucleotides (pharmacology)
• Protein Multimerization (drug effects, genetics)
• Protein Synthesis Inhibitors (pharmacology)