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Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.

ABSTRACT: BACKGROUND:Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear. METHODS:The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model. RESULTS:We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients' lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo. CONCLUSIONS:MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.

SUBMITTER: Yuan S

PROVIDER: S-EPMC6958600 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.

Yuan Shuo S Lin Li-Song LS Gan Rui-Huan RH Huang Li L Wu Xiao-Ting XT Zhao Yong Y Su Bo-Hua BH Zheng Dali D Lu You-Guang YG

BMC cancer 20200114 1

<h4>Background</h4>Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear.<h4>Methods</h4>The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on th ...[more]

PMID: 31937294

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Project description:The molecular mechanisms that underpin invasive ductal breast cancer (IDC) invasion and metastasis are incompletely understood. The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers, where it stimulates the expression of matrix metalloproteinase 9 (MMP9), an important enzyme in the breakdown of the extracellular matrix. However, its role in breast cancer remains poorly understood. This study assessed the clinical significance of MDM2 expression in IDC and used in vitro expression assays to determine the molecular roles of MDM2. Immunohistochemical staining for MMP9 and MDM2 was performed using archived tumor blocks from 321 women who underwent surgical resection for IDC at the First Affiliated Hospital of Nanjing Medical University, China between January 2002 and December 2003. MCF-7 and MDA-MD-231 cell lines were transfected with siRNA targeted against MDM2, or MDM2 was overexpressed using transiently expressed vectors. The invasion, cell migration and proteolytic capabilities of cells that over- or underexpressed MDM2 was then assessed and compared against control cells, in addition to the consequent effects on MMP9 expression using RT-PCR. In vivo, 54.9% and 49.6% of samples were positive for MMP9 and MDM2 expression, respectively, and their expression was significantly correlated (r² = 0.171, P = 0.012). Moreover, MDM2 expression was markedly correlated with disease-free survival (HR 2.56, 95% CI 1.02-6.40, P = 0.038). In vitro, MDM2 overexpression significantly enhanced cell invasion, migration and proteolysis compared with control cells, and the converse effects were observed after MDM2-siRNA treatment. MDM2 overexpression induced MMP9 expression in a dose-dependent manner. Taken together, these results suggest that high levels of MDM2 are associated with a poorer prognosis in IDC. This might result from increased tumor invasiveness due to enhanced MMP9 expression causing increased extracellular matrix breakdown.

Project description:Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial-mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3'-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.

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Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.

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Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.

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