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Inhibition of lncRNA-UCA1 suppresses pituitary cancer cell growth and prolactin (PRL) secretion via attenuating glycolysis pathway.
In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2020-09-09 , DOI: 10.1007/s11626-020-00494-x
Gang Liu 1 , Lu Wang 2 , Yi Li 1
Affiliation  

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 qRT-PCR. 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 lncRNA-UCA1-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.



中文翻译:

lncRNA-UCA1的抑制可通过减弱糖酵解途径抑制垂体癌细胞的生长和催乳激素(PRL)的分泌。

垂体瘤是内分泌肿瘤的一种,发病率和死亡率高。长非编码RNA(lncRNA)是一类长度超过200个核苷酸的非编码RNA。其中,lncRNA-UCA1在多种癌症中高度表达,并在肿瘤进展中起着至关重要的致癌作用。然而,尚未阐明UCA1在人垂体肿瘤中的潜在作用。在这项研究中,分析了lncRNA-UCA1在三十个垂体肿瘤样本和三十个正常垂体组织中的表达。通过葡萄糖摄取和乳酸产生检查癌细胞的糖酵解速率。通过qRT-PCR检测到lncRNA-UCA1表达。通过Western印迹和qRT-PCR测量糖酵解酶的表达。与其他癌症一致,lncRNA-UCA1在垂体肿瘤中高表达。与此同时,我们发现垂体肿瘤的糖酵解高于正常垂体组织。lncRNA-UCA1在大鼠垂体癌细胞系GH3和MMQ中的过表达显着促进了葡萄糖的摄取和乳酸的产生。此外,通过lncRNA-UCA1的外源性过表达,糖酵解关键酶HK2和LDHA的表达显着上调。重要的是,沉默lncRNA-UCA1明显抑制垂体癌细胞的生长和催乳激素(PRL)的分泌。我们报告了更高的lncRNA-UCA1表达与垂体患者血清PRL水平升高有关。最后,通过用糖酵解抑制剂2-DG阻断垂体癌细胞的lncRNA-UCA1促进的糖酵解,我们从体外模型中获得了细胞生长速率和PRL分泌的恢复。在一起 我们的研究表明,lncRNA-UCA1通过上调垂体肿瘤的糖酵解而具有致癌作用。这项研究有助于垂体肿瘤发生的潜在分子机制。

更新日期:2020-09-10
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