Nuclear factor I A promotes temozolomide resistance in glioblastoma via activation of nuclear factor κB pathway
Authors: Ruichun Li
Alafate Wahafu
Maode Wang
Xiao Yu
Wei Wu
Ping Mao
Jia Wang
Jie Zuo
Wanfu Xie
Journal: Life sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glioblastoma; NF-κB; NFIA; Temozolomide resistance; Transcriptional regulation.
Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China., Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China; Center of Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China., The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China., Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China; Center of Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China. Electronic address: .

Abstract:  Aims: To investigate the underlying mechanism by which glioblastoma (GBM) cells gain temozolomide (TMZ) resistance and to clarify novel therapeutic targets and new prognostic biomarkers for GBM. Main methods: A genome-wide hierarchical bi-clustering based on previously published microarray databases identified Nuclear Factor I A (NFIA) as one of the most significantly upregulated genes correlated to TMZ resistance in GBM. Then, the potential biological functions of NFIA in oncogenesis and chemoresistance were clarified by qRT-PCR, Western blotting and in vivo xenograft models with artificially induced TMZ-resistant U87 cells. Additionally, immunohistochemistry (IHC) assays were performed to explore the clinical significance of NFIA in glioma patients. Last, luciferase reporter assay was performed to study the transcriptional regulation of NFIA on the nuclear factor κb (NF-kB) pathway. Key findings: NFIA was correlated with TMZ resistance in GBM. Clinically, elevated NFIA expression was significantly correlated with adverse outcomes of glioma patients, especially in GBM patients. Moreover, NFIA contributed to the acquired TMZ resistance of GBM cells, while suppression of NFIA via lentivirus reduced cell proliferation, tumorigenesis and resistance to TMZ of GBM. Additionally, NFIA promoted transcription activity that regulated the expression of NF-kB. Last, NFIA induced phosphorylation of NF-kB p65 at serine 536, thus inducing TMZ resistance in GBM cells. Altogether, our study suggests that NFIA-dependent transcriptional regulation of NF-kB contributes to acquired TMZ resistance in GBM. Significance: Abnormally activated NFIA-NF-kB signaling was strongly correlated with acquired TMZ resistance and poor prognosis in GBM, and it could be a new therapeutic target for TMZ-resistant GBM. 

Retracted: No

PubPeer comments:
 The ASME paper:  **Online Case Studies and a Process Description for Product Platform Planning**  Anand Srinivasan, Asli Sahin, Janis P. Terpenny, Timothy W. Simpson, Soundar R. T. Kumara, Steven B. Shooter, Robert B. Stone [U Mass Amherst, Virginia Tech, Penn State, Bucknell, University of Missouri-Rolla]  ASME 2005 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, September 24u201328, 2005  https: asmedigitalcollection.asme.org IDETC-CIE proceedings-abstract IDETC-CIE2005 4742Xa 27 311107 copied approximately 95% of the u00a9 2005 ASEE paper published three months earlier:  **An Online Learning Tool For Product Platform Planning**  ASEE Annual Conference Exposition, June 12, 2005  https: peer.asee.org 14516 The ASME version did not cite the earlier ASEE version, did not enclose copied passages in quotation marks, and did not indicate permission of the copyright holder for the content to be republished. The work was funded by the National Science Foundation grants IIS-0325402 ($400,000), IIS- 0325321 ($300,000), IIS-0325279 ($145,0000 and IIS-0325415 ($250,000). 45 CFR u00a7 689 prohibits use of NSF funds for research misconduct. According to UMass: Academic integrity requires that when we use the ideas or words of previous works, we use footnotes, endnotes, or quotation marks, as appropriate. At UMass, we must abide by the Code of Conduct which explicitly forbids plagiarism.  ... Examples for Plagiarism Academic Dishonesty from the u201cAcademic Honesty Guide for Studentsu201d:  u2022 Copying 4+ words consecutively without using quotation marks or citing the source  https: mie.umass.edu sites default files mie MIE_Graduate_Handbook_19-20.pdf According to Bucknell, plagiarism includes: Using even a brief phrase exactly quoted from a source without putting it in quotation marks, indenting it or citing it. https: www.bucknell.edu academics academic-support-responsibility academic-responsibility definitions-procedures-0 Examples of passages copied in the ASME paper are shown below, with the ASME version on the right: ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ,