IKAP/hELP1 deficiency in the cerebrum of familial dysautonomia patients results in down regulation of genes involved in oligodendrocyte differentiation and in myelination
Authors: Channa Maayan
Yoav Smith
Gil Ast
David Cheishvili
Aharon Razin
Journal: Human Molecular Genetics (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: gene; familial dysautonomia; IKBKAP; IKAP/hELP1; neuronal function
Affiliations: Department of Pediatrics, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.

Abstract:  The gene affected in the congenital neuropathy familial dysautonomia (FD) is IKBKAP that codes for the IKAP/hELP1 protein. Several different functions have been suggested for this protein, but none of them have been verified in vivo or shown to have some link with the FD phenotype. In an attempt to elucidate the involvement of IKAP/hELP1 in brain function, we searched for IKAP/hELP1 target genes associated with neuronal function. In a microarray expression analysis using RNA extracted from the cerebrum of two FD patients as well as sex and age matched controls, no genes were found to be upregulated in the FD cerebrum. However, 25 genes were downregulated more than 2-fold in the cerebrum of both the male FD child and female FD mature woman. Thirteen of them are known to be involved in oligodendrocyte development and myelin formation. The down regulation of all these genes was verified by real-time PCR. Four of these genes were also confirmed to be downregulated at the protein level. These results are statistically significant and have high biological relevance, since seven of the downregulated genes in the cerebrum of the FD patients were shown by others to be upregulated during oligodendrocyte differentiation in vitro. Our results therefore suggest that IKAP/hELP1 may play a role in oligodendrocyte differentiation and/or myelin formation. 

Retracted: No

PubPeer comments:
 So obvious...  , 
 This is not the end, there is more to come:  , 
 I just picked a few scratch closure similarities, you ll probably find more. Always remeber, different cells, different conditions!  , 
  Fig 7A from [Niu et al (2019)] ; Fig 8B from [Liu et al (2081)] :  , 
 #2 Surely some mistake, for that  A549 Control image is really **HT29 Control**, according to Fig 3E in [Liu et al (2018)] .  , 
 Fig 3(g):  Fig. 3 Chrysophanol induces cell apoptosis by ROS accumulation in vitro. A549, H738, and HUVEC were treatment with 2 u03bcM and 4 u03bcM for 48 h. ... g The cell apoptosis was detected using Annexin V-FITC PI staining by flow cytometry . Below: Fig 6(b) from [Wang et al (2019)] ,  Soy B promoted more profound apoptotic cell death in ccRCC cells with SphK1 knockdown .  , 
 #1 At left here, Fig 6(b,c) from [Han et al (2019)] .  , 
 #1 Surprise! Here are those tumors again, in Fig 6 of [Gao et al (2017)] .  , 
 At right, Fig 2(e)  The cell invasion was measured by transwell assay . At left, for comparison, Fig 2E,  invasiveness .. of CRC cells from [Wang et al (2018)] .  , 
 29 May 2020 Editoru2019s Note: The Editor in Chief is currently investigating this article as concerns have been raised regarding the integrity of some of data presented here. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full. , 
 #10 If the editors are still investigating, they might find it educational to examine the present Figs 1(g) and 2(i);  and compare them to this previous-prepared montage.  Upper left, Fig 3B from [Sun Zhang (2020)] .  Bufothionine triggers ER stress in U87 and U373 cells. U87 and U373 cells were treated with bufothionine of 50 and 100 u03bcg mL for 48 hours. ... (B). The expression of CHOP, p-PERK, ATF4, and p-eIF2u03b1 in U87 and U373 cells following bufothionine treatment was detected with western blot. Lower left, Fig 2C from [Wei et al (2019)] .  Fur A downregulates SphK1 and inactivates its downstream signaling. ... (C) Fur A suppressed the phosphorylation level of Akt and increased the phosphorylation level of JNK in a dose-dependent manner . Right, FIg 2D from [Deng et al (2020)] .  Chrysophanol promotes apoptosis via the intrinsic pathway in CRC cells... Chrysophanol ...triggered release of mitochondrial cytochrome C into cytosol, increased Bax and PUMA levels and decreased that of Bclu20102 (D) . Other bands are shared between figs but I ran out of coloured crayons. , 
 Retracted [26 November 2020] . -------------------------------- The Editor in Chief retracted this article (Zhang et al. 2020) because of significant concerns regarding a number of Figures presented in this work. After publication, overlap was detected with figures in unrelated articles, some published previously and others within a close time frame. Figure 2A appears to contain the same images that have been published elsewhere with different labels: Figure 6K (Yin et al. 2020) and Figure 3E ((Liu 2018), retracted). Figure 2E images labelled as A549 cells appears to be similar to that published elsewhere with different labels: Figure 4K (Yin et al. 2020) and Figure 2E (Wang et al. 2018). Figure 3G - overlap in images used in this and another unrelated article by other authors (Wang et al. 2019) Figure 6A appears to contain images that have been published elsewhere with different labels: Figure 8B in ((Liu 2018), retracted), Figure 6A (Sun et al. 2020), Figure 7A in (Niu et al. 2019), and Figure 6A ((Gao 2017), retracted). Figure 6E appears to contain images that have been published elsewhere with different labels: Figure 6D (Sun et al. 2020) and Figure 6C (Han et al. 2019). Figure 6K appears to contain images that have been published elsewhere with different labels (Sun et al. 2020) The authors were unable to provide raw data and stated that the figures were produced by a commercial lab hired to perform some of the experiments for this study. Furthermore, the authors stated that some of the data presented were not generated as part of this study. The Editor-in-Chief therefore no longer has confidence in the integrity of the data in this article. All authors agree to this retraction. References - Retracted article: Gao MQ et al. (2017) Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat. Am J Cancer Res 7(7):1501-1514 - Han M, Gao H, Xie J et al (2019) Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway. Acta Pharmacol Sin 40:666u2013676. https: doi.org 10.1038 s41401-018-0159-7 - Retracted article: Liu K. et al. (2018) Hispidulin suppresses cell growth and metastasis by targeting PIM 1 through JAK 2 STAT 3 signaling in colorectal cancer. Cancer Sci. https: doi.org 10.1111 cas.13575 - Niu Y et al (2019) Physcion 8-O-u03b2-glucopyranoside induced ferroptosis via regulating miR-103a-3p GLS2 axis in gastric cancer. Life Sciences V237:116893. https: doi.org 10.1016 j.lfs.2019.116893 - Sun Y, Lv B, Zhang X (2020) Knock-down of LncRNA-XIST induced glioma cell death and inhibited tumorigenesis by regulating miR-137 SLC1A5 axis-mediated ROS production. Naunyn-Schmiedebergu2019s Arch Pharmacol. https: doi.org 10.1007 s00210-020-01831-3 - Wang N et al (2018) Euxanthone suppresses tumor growth and metastasis in colorectal cancer via targeting CIP2A PP2A pathway. Life Sci 209:498u2013506. https: doi.org 10.1016 j.lfs.2018.08.052 - Wang L, Wang J, Zhao H et al (2019) Soyasapogenol B exhibits anti-growth and anti-metastatic activities in clear cell renal cell carcinoma. Naunyn-Schmiedebergu2019s Arch Pharmacol 392:551u2013563. https: doi.org 10.1007 s00210-018-01607-w - Yin J, Yin Q, Liang B et al (2020) Chrysophanol suppresses growth and metastasis of T cell acute lymphoblastic leukemia via miR-9 PD-L1 axis. Naunyn-Schmiedebergu2019s Arch Pharmacol 393:273u2013286. https: doi.org 10.1007 s00210-019-01778-0 - Zhang J, Wang Q, Wang Q et al (2020) Chrysophanol exhibits anti-cancer activities in lung cancer cell through regulating ROS HIF-1a VEGF signaling pathway. Naunyn-Schmiedebergu2019s Arch Pharmacol 393:469u2013480. https: doi.org 10.1007 s00210-019-01746-8 ,