Inhibition of lncRNA-UCA1 suppresses pituitary cancer cell growth and prolactin (PRL) secretion via attenuating glycolys
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Inhibition of lncRNA-UCA1 suppresses pituitary cancer cell growth and prolactin (PRL) secretion via attenuating glycolysis pathway Gang Liu 1 & Lu Wang 2 & Yi Li 1 Received: 3 April 2020 / Accepted: 9 August 2020 / Editor: Tetsuji Okamoto # The Society for In Vitro Biology 2020
Abstract Pituitary tumor is one type of endocrine tumor with high incidence and mortality rates. Long non-coding RNAs (lncRNAs) are a family of non-coding RNAs with longer than 200 nucleotides. Among them, lncRNA-UCA1 is highly expressed in multiple cancers and plays critically oncogenic roles in tumor progressions. However, the potential roles of UCA1 in human pituitary tumor have not been elucidated. In this study, the expressions of lncRNA-UCA1 were analyzed in thirty pituitary tumor samples and thirty normal pituitary tissues. Cancer cell glycolysis rate was examined by glucose uptake and lactate production. The lncRNA-UCA1 expression was detected by qRT-PCR. Glycolysis enzyme expressions were measured by Western blot and qRTPCR. Consistent with other cancers, lncRNA-UCA1 was highly expressed in pituitary tumors. Meanwhile, we found glycolysis of pituitary tumors was higher than normal pituitary tissues. Overexpression of lncRNA-UCA1 in rat pituitary cancer cell lines, GH3 and MMQ, significantly promoted glucose uptake and lactate production. In addition, expressions of the glycolysis key enzymes, HK2 and LDHA, were significantly upregulated by exogenous overexpression of lncRNA-UCA1. Importantly, silencing lncRNA-UCA1 obviously inhibited pituitary cancer cells growth and prolactin (PRL) secretion. We report higher lncRNA-UCA1 expression is associated with higher serum PRL level in pituitary patients. Finally, by blocking the lncRNAUCA1-promoted glycolysis of pituitary cancer cells by glycolysis inhibitor, 2-DG, we obtained recovery of cell growth rate and PRL secretion from an in vitro model. Taken together, our investigation revealed an oncogenic role of lncRNA-UCA1 through upregulating glycolysis of pituitary tumors. This study contributes to underlying molecular mechanisms of the tumorigenesis of pituitary tumors. Keywords Pituitary tumor . Prolactin . lncRNA-UCA1 . Warburg effect . Glycolysis
Introduction Pituitary adenoma, one type of endocrine tumor which has increased incidence in recent years, is the third most common intracranial tumor behind glioma and meningioma (Mete and Lopes 2017). Currently, chemo- and radio-therapies and surgical removal are the routine therapeutic strategies for pituitary adenoma (Dai et al.2019; Trifiletti et al.2019). Among multiple types of pituitary adenoma, prolactinomas are one of the most prevalent subtypes which lead to serious infertility among young women by elevating the serum prolactin (PRL) * Gang Liu [email protected] 1
Department of Internal Medicine, Tianjin Huanhu Hospital, Tianjin 300060, People’s Republic of China
2
Department of Emergency Medicine, Tianjin Third Central Hospital, Tianjin 300060, People’s Republic of China
level (Cocks Eschler et al.2018). Thus, the emergent ta
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