MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκBα negative feedback loop
Authors: Lili Jiang
Jueheng Wu
Mian He
Lishan Fang
Mengfeng Li
Chuyong Lin
Jun Li
Zhe Ying
Xiao Yan
Libing Song
Baixue Chen
Journal: Journal of Clinical Investigation (2012)
Discipline: CLINICAL MEDICINE
Keywords: NF-κB; IκB; microRNA-30e*; glioma; gene expression
Affiliations: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Abstract:  Constitutive activation of NF-κB is a frequent event in human cancers, playing important roles in cancer development and progression. In nontransformed cells, NF-κB activation is tightly controlled by IκBs. IκBs bind NF-κB in the cytoplasm, preventing it from translocating to the nucleus to modulate gene expression. Stimuli that activate NF-κB signaling trigger IκB degradation, enabling nuclear translocation of NF-κB. Among the genes regulated by NF-κB are those encoding the IκBs, providing a negative feedback loop that limits NF-κB activity. How transformed cells override this NF-κB/IκB negative feedback loop remains unclear. Here, we report in human glioma cell lines that microRNA-30e* (miR-30e*) directly targets the IκBα 3ι-UTR and suppresses IκBα expression. Overexpression of miR-30e* in human glioma cell lines led to hyperactivation of NF-κB and enhanced expression of NF-κB-regulated genes, which promoted glioma cell invasiveness in in vitro assays and in an orthotopic xenotransplantation model. These effects of miR-30e* were shown to be clinically relevant, as miR-30e* was found to be upregulated in primary human glioma cells and correlated with malignant progression and poor survival. Hence, miR-30e* provides an epigenetic mechanism that disrupts the NF-κB/IκBα loop and may represent a new therapeutic target and prognostic marker. 

Retracted: No

PubPeer comments:
 Figure 8A and supplemental Figure 5E. Image reuse with different photo catching condition. ![file] , 
 Image reuse in two papers with obvious manipulation. ![file] , 
 #2 Dear Sir or Madam, u00a0 Your comment is highly appreciated. u00a0We are taking it seriously and are currently looking into the data associated with the question raised. u00a0 Sincerely, Jun Li , 
 Here is another one. ![file] , 
 Dear Apareia Labialis, Your comment is highly appreciated. We are taking it seriously and are currently looking into all original the data associated with these two articles. Sincerely, Jun Li , 
 Corrigendum: The authors recently became aware that the image presented in the original Supplemental Figure 5D as miR-30e* PGC#2 was identical to the image in Supplemental Figure 8E, NC U87MG-miR-30e 30e*, and that the image presented in the original Supplemental Figure 5E as miR-30e* inhibitor PGC#2 was identical to the image in Figure 8A, miR-30e* inhibitor U87MG. After review of the original data, the authors determined that the errors were made in Supplemental Figure 5E and Supplemental Figure 5D. An institutional review committee concluded that the errors in Supplemental Figure 5D and Supplemental Figure 5E were inadvertent and recommended correction. The authors provided the correct version of Supplemental Figure 5D and Supplemental Figure 5E with data obtained from repeated experiments. The correct version is shown below and in the updated supplemental data. ![file] , 
 The concern that two images were reused in two papers has not been addressed. Do the institutional review committee and the journal editorial office know thisuff1f , 
 An additional concern about Figure 9A: * Red boxes: The enlarged MMP9 and VEGF-C panels appear to overlap, albeit shown at different exposures, and the latter does not match the lower magnification version. ![file] , 
 An additional concern about Figure 7A: * Blue boxes: Two panels displaying different cells and stainings appear to show an overlap. ![file] Detail view: ![file] ,