Long non-coding RNA growth arrest-specific transcript 5 is involved in ovarian cancer cell apoptosis through the mitochondria-mediated apoptosis pathway

Gao,Jiayin; Liu,Meimei; Zou,Yiting; Mao,Min; Shen,Tingting; Zhang,Chen; Song,Shasha; Sun,Meiling; Zhang,Song; Wang,Beidi; Zhu,Daling; Li,Peiling

doi:10.3892/or.2015.4318

Long non-coding RNA growth arrest-specific transcript 5 is involved in ovarian cancer cell apoptosis through the mitochondria-mediated apoptosis pathway

Authors:
- Jiayin Gao
- Meimei Liu
- Yiting Zou
- Min Mao
- Tingting Shen
- Chen Zhang
- Shasha Song
- Meiling Sun
- Song Zhang
- Beidi Wang
- Daling Zhu
- Peiling Li
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Affiliations: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China, Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, P.R. China, Department of Nursing, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China, Department of Medical Service, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
Published online on: October 1, 2015 https://doi.org/10.3892/or.2015.4318
Pages: 3212-3221

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Abstract

The present study investigated the underlying role of growth arrest-specific transcript 5 (GAS5) in epithelial ovarian cancer (EOC), which is the main cause of death in women with malignant tumor of the genital system. In vivo GAS5 expression in 60 EOC specimens was evaluated by quantitative reverse transcription (qRT)-PCR, which was used to study the differences of GAS5 expression between EOC tissues and normal ovarian epithelium. In vitro GAS5 overexpression was applied to discover the biological functions in EOC cell lines. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide and colony formation assays were employed to investigate the effect on proliferation. The function of apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and JC-1 probe staining, and migration and invasion were detected by Transwell assay. The data show that no significant differences of GAS5 expression were observed between normal ovarian epithelium and benign epithelial lesions; however, GAS5 expression was lower in EOC tissues compared with normal ovarian epithelial tissues (6.44-fold), which was closely related to lymph node metastasis (P=0.025) and tumor node metastasis stage (P=0.035). Moreover, exogenous GAS5-inhibited proliferation promoted apoptosis and decreased migration and invasion in ovarian cancer cells. Finally, through mitochondrial potential and western blot analyses, GAS5 could disrupt mitochondrial membrane potential and promote BAX, BAK, cleaved-caspase 3 and cleaved-caspase 9 expression. Taken together, the findings of the present study revealed that GAS5 is downregulated in EOC specimens, and GAS5 inhibits EOC cell proliferation, migration and invasion, and promotes cell apoptosis. GAS5 can serve as a novel therapeutic target in patients with EOC.

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