Human leptin protein induces proliferation of A549 cells via inhibition of PKR-like ER kinase and activating transcription factor-6 mediated apoptosis
Authors: Yan Sun
Qun Lai
Journal: Yonsei Medical Journal (2013)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; ER stress; TRAF2; XPB1; cell growth
Affiliations: Department of Thoracic Surgery, General Hospital of Zaozhuang Mining Group, Shandong, Zaozhuang, China.

Abstract:  Purpose: To investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer. Materials and methods: The influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2α, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR. Results: The expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. Furthermore, CHOP expression was inhibited upon leptin expression in A549, LPT-PeP and LPT-EX cells. Conclusion: Leptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. This blocking is triggered by p-Perk and ATF6 via inhibition of CHOP expression. 

Retracted: No

PubPeer comments:
 Panels from Figure 3 in this paper appear to also be visible in a different paper by different authors from a different institute. That paper is:  Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration - Lijun Shi et al. - Experimental and Therapeutic Medicine (2015) - doi: 10.3892 etm.2015.2501. The marked image below shows the similarities between the panels in both papers with square colored boxes, as well as repetitive elements between panels, as shown with colored ellipses. I have only marked these for the Shi 2015 paper but they are valid for this paper as well. ![file] , 
 Focusing in this paper s Figure 3, here is that figure again, with boxes of the same color to draw attention to areas that look similar. ![file] , 
 In addition to the similarity of Figure 3 of this paper to the 2015 Shi paper, Figure 3 and several other figures look similar to figures in a third paper, by Wang et al., Human Leptin Triggers Proliferation of A549 Cells via Blocking Endoplasmic Reticulum Stress-Related Apoptosis, Biochemistry (Moscow), 2013, Vol. 78, No. 12, pp. 1333-1341., DOI: 10.1134 S0006297913120031 That paper has been retracted, but it is worth pointing out the similarities of the flow cytometry figures in 3 otherwise unrelated papers. ![file] ,