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Linc02527 促进妊娠肝内胆汁淤积症中的自噬。

Linc02527 promoted autophagy in Intrahepatic cholestasis of pregnancy.

机构信息

Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

出版信息

Cell Death Dis. 2018 Sep 24;9(10):979. doi: 10.1038/s41419-018-1013-z.

DOI:10.1038/s41419-018-1013-z
PMID:30250023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6155230/
Abstract

LncRNA plays a crucial role in human disease. However, the expression and function of LncRNA in ICP(Intrahepatic cholestasis of pregnancy) is still not fully elucidated. In this study, we found Linc02527 was increased expression in placenta and serum of ICP patients. Ectopically expression of Linc02527 promoted autophagy and proliferate in HTR8 cells. Silencing Linc02527 suppressed the autophagy and proliferate in HTR8 cells. Mechanically study revealed that Linc02527 regulated the expression of ATG5 and ATG7 by sponging miR-3185. Linc02527 directly binding to YBX1 and activated P21. The growth of C57 mouse was retarded when autophagy was activated. In normal condition, inhibited autophagy using chloroquine did not affect the growth of C57 mouse. However, in the condition of autophagy was activated, inhibited autophagy using chloroquine can improve the growth of C57 mouse. Overall, the results of this study identified Linc02527 as a candidate biomarker in ICP and a potential target for ICP therapy. Chloroquine was a potential drug for ICP therapy.

摘要

长链非编码 RNA 在人类疾病中发挥着关键作用。然而,长链非编码 RNA 在妊娠肝内胆汁淤积症(ICP)中的表达和功能仍未完全阐明。在本研究中,我们发现 Linc02527 在 ICP 患者的胎盘和血清中表达增加。Linc02527 的异位表达促进了 HTR8 细胞的自噬和增殖。沉默 Linc02527 抑制了 HTR8 细胞的自噬和增殖。机制研究表明,Linc02527 通过海绵吸附 miR-3185 调节 ATG5 和 ATG7 的表达。Linc02527 直接结合 YBX1 并激活 P21。当自噬被激活时,C57 小鼠的生长会受到阻碍。在正常情况下,使用氯喹抑制自噬不会影响 C57 小鼠的生长。然而,在自噬被激活的情况下,使用氯喹抑制自噬可以改善 C57 小鼠的生长。总的来说,这项研究的结果表明 Linc02527 是 ICP 的候选生物标志物和 ICP 治疗的潜在靶点。氯喹可能是 ICP 治疗的一种潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/5af6b7417d71/41419_2018_1013_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/73527a5d50cd/41419_2018_1013_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/d0ac18812a77/41419_2018_1013_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/e8adc078a2b5/41419_2018_1013_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/c5168906e381/41419_2018_1013_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/8244b55c5413/41419_2018_1013_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/565d236a5e9e/41419_2018_1013_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/5af6b7417d71/41419_2018_1013_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/73527a5d50cd/41419_2018_1013_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/d0ac18812a77/41419_2018_1013_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/e8adc078a2b5/41419_2018_1013_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/c5168906e381/41419_2018_1013_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/8244b55c5413/41419_2018_1013_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/565d236a5e9e/41419_2018_1013_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/6155230/5af6b7417d71/41419_2018_1013_Fig7_HTML.jpg

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