Synergistic effects of co-expression plasmid‑based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo
Authors: Kai Liu
Songyang Liu
Yingchao Wang
Wei Zhang
Bai Ji
Yahui Liu
Journal: Oncology Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: ADAM10; GRIM-19; HCC; therapy; siRNA
Affiliations: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.

Abstract:  A disintegrin and metalloproteinase 10 (ADAM10) has been demonstrated to correlate with hepatocellular carcinoma (HCC) grade and clinical outcome and its potential as a target for HCC therapy has been established. Gene associated with retinoid-interferon-induced mortality 19 (GRIM-19), a signal transducer and activator of transcription 3 (Stat3)-inhibitory protein, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. In the present study, we investigated whether a combined treatment with ADAM10-specific siRNA and GRIM19 gene could have an enhanced anticancer effectiveness on HCC in vitro and in vivo. We developed a dual expression plasmid that co-expressed ADAM10-specific siRNA and GRIM19, to evaluate its effects on HCC growth. Our results showed that simultaneous expression of ADAM10-specific siRNA and GRIM19 (pSi-ADAM10-GRIM19) in HepG2 cancer cells significantly inhibited the proliferation, migration and invasion, and induced cell apoptosis in vitro, and it also suppressed tumor growth in a nude mouse model when compared to the controls, either ADAM10-specific siRNA or GRIM-19 alone. In summary, our data demonstrated that a combined strategy of co-expressed ADAM10-specific siRNA and GRIM19 synergistically and more effectively suppressed HCC tumor growth, and has therapeutic potential for the treatment of HCC. 

Retracted: Yes

PubPeer comments:
 This paper shares some images with [another paper](http: doi.org 10.3892 or.2013.2650) that has no common authors: ![file] Figures 6 and 8 of Shao Yuan 2013: ![file] ![file] , 
 So the images appear in -  [Downregulation of ADAM10 expression inhibits metastasis and invasiveness of human hepatocellular carcinoma HepG2 cells]  (Yue et al 2013): retracted from BioMed Research International. -  [ADAM10 is overexpressed in human hepatocellular carcinoma and contributes to the proliferation, invasion and migration of HepG2 cells]  (Yuan et al 2013): cited as the reason for that retraction. -  [Synergistic effects of co-expression plasmidu2011based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo]  (Liu et al 2014). The present paper. Have I missed anything? , 
 Figs 2C *[left]* and 5 *[right]*. Blue and green boxes mark some unexpected similarities. There may have been some error during figure assembly. ![file] For comparison: Figs 4C, 5D from [Zhang et al (2014)] . ![file] For further comparison: Figs 3C, 7 from [Liu et al (2014)] . ![] , 
 #3 Figs 2C and 5 again, now focusing on two bands marked in violet and bright green. ![file] Unexpectedly similar to bands in Fig 6 of [Zhang et al (2014)] ,  Effect of CXB and XIAP-shRNA alone or in combination on the PI3K AKT signaling pathway in A549 cells. Phosphorylation activation pattern of PI3K and Akt were measured by western blotting 24 h after treatment with CXB and XIAP-shRNA alone or in combination in the A549 cell line. Blots were reprobed for u03b2-actin to normalize each lane for protein content . ![file] No authors in common. , 
 *[left]* Fig 7A.  Images of tumor tissue with different plasmid treatments collected after sacrifice at day 35. *[right]* Fig 7A from [Zhang et al (2015)] .  Images of the tumor tissues from the different groups . ![file] Surprising similarities after a 180-deg flip. Also, *[left]* Fig 5A from [Li et al (2015)] .  Images of tumor tissue with different group collected after sacrifice at day 21 . *[right]* Fig 7 from [Wu et al (2015)] .  miR-128 inhibits tumor growth tumorigenicity in vivo by inhibiting IRSI. (A) Images of tumors derived for different groups . ![file] , 
 Retracted [26 November] . -------------------------- Following the publication of the above paper, it was drawn to the Editoru2019s attention by a concerned reader that various data featured in several of the figures were strikingly similar to data appearing in different form in other articles by different authors. An independent enquiry was launched by the Editorial Office, which revealed that cell migration assay data featured in Fig. 5A and C of the above article had been included in another article written by different authors submitted for publication some 12 months previously. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to *Oncology Reports*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,