Downregulation of matrix metalloproteinase 9 by small interfering RNA inhibits the tumor growth of ovarian epithelial carcinoma in vitro and in vivo
Authors: Manhua Cui
Meiru Fang
Jingyan Tian
Fengjun Guo
Lin Yang
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Matrix metalloproteinase 9; MMP-9; ovarian carcinoma; RNA interference; proliferation
Affiliations: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China., Department of Urology, The Second Division of The First Hospital, Jilin University, Changchun, Jilin 130031, P.R. China., Siping Health School of Jilin Province, Siping, Jilin 136000, P.R. China.

Abstract:  Matrix metalloproteinase 9 (MMP-9) is upregulated in various types of malignancy, including human ovarian carcinomas. It promotes invasion, metastasis, growth and the survival of malignant cells. However, relatively little is known about the role of MMP9 in epithelial ovarian carcinoma. Therefore, the aim of the present study was to determine the effects of targeting this molecule on ovarian carcinoma progression. A plasmid, psi-MMP-9, carrying a short hairpin RNA against MMP-9 gene expression was constructed and transfected into the human ovarian cancer cell line SKOV3 using a human U6 promoter-driven DNA template approach to determine the effect of MMP-9 gene RNA interference (RNAi) on the proliferation, apoptosis, migration, invasion and tumorigenicity of the human ovarian carcinoma cells. The results demonstrated that siRNA-mediated knockdown of MMP-9 in the human ovarian cancer cell line SKOV3 inhibited cell proliferation, migration and invasion in vitro. The results also demonstrated that downregulation of MMP-9 led to cell apoptosis in SKOV3 cells, inhibited the expression of anti-apoptotic molecules, including B cell lymphoma-2, survivin and X-linked inhibitor of apoptosis protein, and enhanced the activity of capsase-3 and caspase-8. In addition, knockdown of MMP-9 inhibited tumorigenicity in nude mice. Taken together, MMP-9 gene RNAi in ovarian carcinoma cells inhibited proliferation, migration and invasion, induced cell apoptosis in vitro and suppressed tumor growth in nude mice. These results suggest that MMP-9 is an ovarian cancer-associated gene and is a potential target for therapeutic anti-cancer drugs. 

Retracted: Yes

PubPeer comments:
 Figs 1B, 3A.  Western blot analysis of MMP-9 protein expression 72 h after plasmid transfection ;  Survivin, XIAP and Bcl-2 expression was determined by western blot analysis. ![file] Colored boxes mark appearances of the same bands in Fig 5C, [Li et al (2014)] . ![] Fig 1B from [Gao et al (2015)] .  Following stimulation with LPS, ADAM15 protein was evaluated using western blotting . ![] Fig 5A from Gao et al. ![file] Other manifestations of the bands are linked in those threads. , 
 Retracted [31 August 2021] . ------------------------------- Following the publication of this paper, the authors contacted the Editorial Office to request that the article be retracted on account of an inability to obtain consistent results after having repeated the experiments portrayed in Figs. 1B and 3B. Independently, it was drawn to the Editoru2019s attention that certain of the western blotting data shown in these figures were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these other articles were under consideration for publication at the same time as the above article was submitted for publication to *Molecular Medicine Reports*, the Editor has agreed to the authorsu2019 request that this article should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. ,