title: Upregulation of GRIM-19 suppresses the growth of oral squamous cell carcinoma in vitro and in vivo.
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.
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
authors.forename: Minghe
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
authors.forename: Chongyang
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human