Exosome-transmitted lncRNA H19 inhibits the growth of pituitary adenoma.
Exosome-transmitted lncRNA H19 inhibits the growth of pituitary adenoma.
复制标题
外泌体传输的 lncRNA H19 抑制垂体腺瘤的生长
DOI：
10.1210/jc.2019-00536
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发表时间：
2019-12
期刊：
影响因子：
--
通讯作者：
Zhe Bao Wu
中科院分区：
文献类型：
--
作者：
Yong Zhang;Yan Ting Liu;Hao Tang;Wan Qun Xie;Hong Yao;Wei Ting Gu;Yong Zhi Zheng;Han Bing Shang;Yu Wang;Yong Xu Wei;Ze Rui Wu;Zhe Bao Wu
上下文
CONTEXT
Our previous study demonstrated that the expression of long non-coding RNA H19 (lncRNA H19) was frequently downregulated in human primary pituitary adenomas and negatively correlated with tumor progression. However, the role of exosomal lncRNA H19 in the inhibition of pituitary tumor growth remains unclear.
OBJECTIVE
To investigate whether exosomal H19 could be transported across the cell membrane to exert its inhibitory effect on pituitary tumor growth.
METHODS
The empty lentivirus (EV) GH3 cells with or without H19-overexpression were used to establish a xenograft model. Isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking and Western blotting. The expression levels of serum exosomal H19 from 200 healthy subjects and 206 patients with various subtypes of pituitary tumors were detected by ultracentrifugation and qRT-PCR.
RESULTS
The growth of distal tumor cells was inhibited by transferring exosomal H19, which could be transported through cell membrane and exert its inhibitory effect. Cabergoline increased H19 expression and played a synergic therapeutic effect with exosomal H19. Exosomal H19 inhibited phosphorylation of the mTORC1 substrate 4E-BP1. Of Note, the expression level of exosomal H19 in the patients with all subtypes of pituitary tumors was significantly lower than that in the healthy subjects. The change of plasma exosomal H19 level may be correlated with the prognosis or drug response of the patients.
CONCLUSION
Exosomal H19 inhibits the growth of distal pituitary tumors through inhibiting 4E-BP1 phosphorylation. Plasma exosomal H19 may serve as an important biomarker for predicting medical response of patients with prolactinomas.
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16
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