Lactate dehydrogenase is correlated with clinical stage and grade and is downregulated by si‑SAΤB1 in ovarian cancer

Xiang,Jiangdong; Zhou,Lina; Zhuang,Yan; Zhang,Jin; Sun,Ya; Li,Shuangdi; Zhang,Zhenbo; Zhang,Gao; He,Yinyan

doi:10.3892/or.2018.6658

Lactate dehydrogenase is correlated with clinical stage and grade and is downregulated by si‑SAΤB1 in ovarian cancer

Authors:
- Jiangdong Xiang
- Lina Zhou
- Yan Zhuang
- Jin Zhang
- Ya Sun
- Shuangdi Li
- Zhenbo Zhang
- Gao Zhang
- Yinyan He
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Affiliations: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, P.R. China, The Wistar Institute, Philadelphia, PA 19104, USA
Published online on: August 17, 2018 https://doi.org/10.3892/or.2018.6658
Pages: 2788-2797

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Abstract

Lactate, which is regulated by gene expression, is largely believed to favor tumor growth and survival. Elevated lactate dehydrogenase (LDH) is a negative prognostic biomarker because it is a key enzyme involved in cancer metabolism. Our previous study revealed that special AT‑rich‑binding protein 1 (SATB1), a genome‑organizing protein, was strongly associated with high metastasis rates in ovarian cancer. However, its underlying molecular mechanisms in ovarian cancer are unclear. In the present study, we investigated whether SATB1 modulated LDH expression and examined the relationship between SATB1 and LDH in ovarian cancer. We employed transient siRNA‑mediated knockdown of SATB1 in ovarian cancer and explored the effects of this knockdown on the expression levels of key glucose metabolism‑related enzyme genes (G6PD, LDH, MDH1, PFK1 and TGM1) and the glucose metabolism‑related protein monocarboxylate transporter 1 (MCT1). We comprehensively analyzed the cellular and molecular role of LDH in ovarian cancer to determine whether it could be a conventional clinicopathological parameter. SATB1 knockdown significantly downregulated both LDH and MCT1 levels and markedly upregulated BRCA1 and BRCA2 levels in ovarian cancer cells (P<0.05). Serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumors (P<0.05). LDH levels at different stages and grades differed significantly in ovarian cancer. Survival curves revealed that higher LDH expression was correlated with shorter survival (P<0.05). SATB1 may reprogram energy metabolism in ovarian cancer by regulating LDH and MCT1 levels to promote metastasis. Serum LDH levels presented diagnostic accuracy with high specificity and may have potential as a conventional clinicopathological parameter for ovarian cancer.

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