Silence of MACC1 expression by RNA interference inhibits proliferation, invasion and metastasis, and promotes apoptosis in U251 human malignant glioma cells

Sun,Longfeng; Li,Gang; Dai,Bing; Tan,Wei; Zhao,Hongwen; Li,Xiaofei; Wang,Aiping

doi:10.3892/mmr.2015.3886

Silence of MACC1 expression by RNA interference inhibits proliferation, invasion and metastasis, and promotes apoptosis in U251 human malignant glioma cells

Authors:
- Longfeng Sun
- Gang Li
- Bing Dai
- Wei Tan
- Hongwen Zhao
- Xiaofei Li
- Aiping Wang
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Urology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China, Department of Emergency Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Nursing, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: June 3, 2015 https://doi.org/10.3892/mmr.2015.3886
Pages: 3423-3431
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The overexpression of metastasis‑associated in colon cancer 1 (MACC1) has been demonstrated not only in colon cancer, but also in various other types of cancer. Gliomas are the most common type of intracranial tumors, and recent studies have reported MACC1 to be involved in human glioma progression. The present study aimed to investigate the effects of MACC1 expression silencing in glioma cells using RNA interference, in order to determine the underlying biological mechanisms of glioma progression, including proliferation, apoptosis, invasion and metastasis. The expression levels of MACC1 were determined in various types of U251 glioma cells using western blot analyses. MACC1‑specific short hairpin RNA (shRNA) was used to silence the expression of MACC1 in the U251 cells. The results obtained following MACC1 silencing demonstrated a significant inhibition of cell proliferation, invasion and migration, as well as a marked enhancement of apoptosis. MACC1 shRNA‑induced inhibition of cell proliferation was observed by colony forming and MTT assays, and cell apoptosis was measured using flow cytometry and Hoechst staining. In addition, inhibition of cell invasion and migration was assessed using wound healing and transwell assays. Western blotting and fluorescence‑activated cell sorting (FACS) revealed a G0/G1 phase cell cycle arrest regulated by cyclins D1 and E; cell apoptosis regulated by caspase‑3; and cell invasion and migration regulated by matrix metalloproteinases 2 and 9, respectively. The present study demonstrated that the expression levels of MACC1 were significantly correlated with the biological processes underlying glioma cell proliferation, invasion and metastasis. Therefore, MACC1 may serve as a promising novel therapeutic target in human glioma. Notably, the inhibition of MACC1 expression by shRNA may prove to be an effective genetic therapeutic strategy for glioma treatment.

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