Upregulation of GRIM-19 suppresses the growth of oral squamous cell carcinoma in vitro and in vivo
Authors: Zhihong Li
Chongyang Liang
Fei Sun
Minghe Li
Chengmin Han
Wei Huang
Journal: Oncology Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: STAT3; GRIM-19; oral squamous cell carcinoma; tumor growth; cell proliferation
Affiliations: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China., Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract:  Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) and its upregulation contribute to the progression and metastasis of several different tumor types. The gene associated with retinoid‑interferon‑induced mortality-19 (GRIM-19) is known to functionally interact with STAT3 and inhibit its transcriptional activity. It has been reported that upregulation of genes associated with GRIM-19 can significantly reduce the tumor growth of several types of tumors. However, little is known in regards to its role in oral squamous cell carcinoma (OSCC). In the present study, a recombinant eukaryotic expression plasmid carrying GRIM-19 was constructed to evaluate its effects on OSCC cancer growth. Upregulation of GRIM-19 in OSCC cells significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Moreover, we found that upregulation of GRIM-19 reduced cyclin D1, Bcl-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) expression whose protein is involved in STAT3 activation. Taken together, these findings suggest that GRIM-19 plays an inhibitory role in the progression of OSCC, and contribute to the future development of STAT3-based gene therapeutic approaches for OSCC. 

Retracted: No

PubPeer comments:
 Fig 5C.  Western blotting of the expression of STAT3 target genes (Bcl-2, cyclin D1 and VEGF) in HSC3 cells using specific antibodies against the indicated proteins following treatment with the indicated plasmid. Blots were reprobed for u03b2-actin to normalize each lane for protein content . ![file] I have flipped the VEGF band through 180 deg for ease of comparison with Figs 3C, 7 from [Liu et al (2014)] ... ![file] ... and with Figs 4C, 5D from [Zhang et al (2014)] . ![file] Further comparison with Figs 2C *[left]* and 5 *[right]* from [Liu et al (2014b)] . ![] UPDATE: Another sighting! Fig 4 from [Li et al (2015)] . ![] , 
 *[left]* Fig 1C.  Western blotting of GRIM-19 protein expression 72 h after plasmid transfection. *[right]* Fig 5 from [Qian et al (2014)] .  Effect of cetuximab (CET) in combination with celecoxib (CXB) on epidermal growth factor receptor (EGFR) downstream signaling molecules. Treatment of cells for 24 h with CET in combination with CXB further reduced the expression levels of p-EGFR, p-PI3K and p-Akt in the HSC3 cell line. ![file] ----------------------------------------------- *[left]* Fig 1C again. *[right]* Fig 4D from [Zhang et al (2015)] .  Expression of MMP-2 and MMP-9 in A549 cells was determined by western blotting. ![file] ,