Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
Authors: Peng-Yuan Wang
Tongtong Zou
Yu-Hong Cui
Xian Zhang
Myriam Gorospe
Lan Liu
Lan Xiao
Jaladanki N Rao
Jian-Ying Wang
Journal: Nucleic Acids Research (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: XIAP; HuR; mRNA stability; intestinal epithelial cells; apoptosis
Affiliations: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21224, USA.

Abstract:  The X chromosome-linked inhibitor of apoptosis protein (XIAP) is the most potent intrinsic caspase inhibitor and plays an important role in the maintenance of intestinal epithelial integrity. The RNA binding protein, HuR, regulates the stability and translation of many target transcripts. Here, we report that HuR associated with both the 3'-untranslated region and coding sequence of the mRNA encoding XIAP, stabilized the XIAP transcript and elevated its expression in intestinal epithelial cells. Ectopic HuR overexpression or elevated cytoplasmic levels of endogenous HuR by decreasing cellular polyamines increased [HuR/XIAP mRNA] complexes, in turn promoting XIAP mRNA stability and increasing XIAP protein abundance. Conversely, HuR silencing in normal and polyamine-deficient cells rendered the XIAP mRNA unstable, thus reducing the steady state levels of XIAP. Inhibition of XIAP expression by XIAP silencing or by HuR silencing reversed the resistance of polyamine-deficient cells to apoptosis. Our findings demonstrate that HuR regulates XIAP expression by stabilizing its mRNA and implicates HuR-mediated XIAP in the control of intestinal epithelial apoptosis. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. , 
 An additional concern: Figure 2 shows two sets of two panels that not only both match the 100 photos in the Stock Photo library, but that also appear to show the same photo and (in one case) overlap with each other. Figure 2D (migration) and Figure 2E (invasion) both are showing the  TW14 - Necklace and  TW06 - The Catch and the Map photos. In case of the TW06 photos, an overlap is visible, as shown with red boxes. In the TW14 case, two different field were chosen that are not overlapping. ![file] And here is a screenshot of the  TW14 - Necklace composite photo, with blue and green circles showing the position of the left panels in Figure 2D and Figure 2E, respectively. ![file] ,