Downregulation of MACC1 inhibits invasion, migration and proliferation, attenuates cisplatin resistance and induces apoptosis in tongue squamous cell carcinoma

Li,Hai-Feng; Liu,Ye-Qing; Shen,Zhuo-Jian; Gan,Xiang-Feng; Han,Jing‑Jing; Liu,Yun-Yun; Li,Hai-Gang; Huang,Zhi-Quan

doi:10.3892/or.2014.3612

Downregulation of MACC1 inhibits invasion, migration and proliferation, attenuates cisplatin resistance and induces apoptosis in tongue squamous cell carcinoma

Authors:
- Hai-Feng Li
- Ye-Qing Liu
- Zhuo-Jian Shen
- Xiang-Feng Gan
- Jing‑Jing Han
- Yun-Yun Liu
- Hai-Gang Li
- Zhi-Quan Huang
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Affiliations: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China, Department of Cardio-Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China, Department of Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China, Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
Published online on: November 21, 2014 https://doi.org/10.3892/or.2014.3612
Pages: 651-660

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Abstract

The aim of the present study was to investigate the expression and function of metastasis-associated in colon cancer 1 (MACC1) in tongue squamous cell carcinoma (TSCC) and its relationship with the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147). Levels of MACC1 and EMMPRIN expression were analyzed in 65 paraffin‑embedded tissue specimens of TSCC and in the adjacent non-cancerous tissues using immunohistochemistry (IHC). MACC1 expression was highly associated with lymphatic metastasis and EMMPRIN expression. Overexpression of MACC1 was significantly correlated with poor overall patient survival. A small interfering RNA (siRNA) was delivered into TSCCA cells to downregulate MACC1 expression. The CCK-8 assay showed that TSCCA cell proliferation was markedly reduced and that cisplatin resistance was attenuated. The suppression of MACC1 promoted the apoptosis of the TSCCA cell line. A Transwell experiment demonstrated that the migration and invasion abilities of the TSCCA cells were extremely downregulated. An ELISA experiment and western blotting revealed that the secretion of urokinase-type plasminogen activator system (uPA) in the supernatant of the culture medium and uPA expression were significantly reduced. Experiments revealed that the secretion of metalloproteinase 2 (MMP2) in the supernatant of the culture medium and MMP2 expression were not affected. MACC1 may serve as a novel biomarker and therapeutic target for TSCC.

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