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长链非编码RNA LINC01279通过靶向HOXA10诱导子宫内膜异位症。

Lnc-RNA LINC01279 induces endometriosis via targeting of HOXA10.

作者信息

Liu Liling, Cheng Junping, Wei Fu, Pang Lihong, Zhi Zhifu, Yang Wenmei, Tan Weihong

机构信息

Department of Reproductive Medicine and Genetics Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, China.

出版信息

J Obstet Gynaecol Res. 2021 May;47(5):1825-1836. doi: 10.1111/jog.14723. Epub 2021 Mar 3.

DOI:10.1111/jog.14723
PMID:33657670
Abstract

AIM

To explore the regulatory role and molecular mechanism of lncRNA-LINC01279 in endometriosis (EMs).

METHODS

Between September 2018 and July 2019, 20 EMs patients and 20 healthy subjects were recruited to detect the expression of lncRNA-LINC01279 in EMs and in normal endometrium via qRT-PCR. Autograft was used to establish EMs models on Spraque-Dawley (SD) rats, which was followed by taking volume measurements of EMs endometrium and observing pathological changes in the morphology of EMs via hematoxylin and eosin (H&E) staining. The qRT-PCR technique was further carried out to determine mRNA expression of lncRNA-LINC01279 and HOXA10 in the serum of EMs rats and LINC01279 shRNA-transfected rats, while the protein expression of HOXA10 was determined using a Western blot.

RESULTS

EMs patients presented with upregulation of lncRNA-LINC01279 and downregulation of HOXA10 (p < 0.01 or 0.001). Online predictions further revealed that lncRNA-LINC01279 regulated the expression of HOXA10 via miRNA-135b. In EMs models, it was observed that there were a significantly enlarged endometrium and poor pathological morphology, significant upregulation of lncRNA-LINC01279, and downregulation of miR-135b and HOXA10 in serum (p < 0.05, 0.01 or 0.001). In the lncRNA-LINC01279 shRNA group, EMs rats, following treatment, had a sharp decrease in the volume of EMs endometrium, and an improvement in pathological morphology, while lncRNA-LINC01279 was downregulated, with upregulation of miR-135b and HOXA10 (p < 0.05, 0.01 or 0.001).

CONCLUSION

LncRNA-LINC01279, by the mechanism of targeting miR-135b, has the potential to downregulate the expression of HOXA10, and therefore, can promote the development and progression of EMs.

摘要

目的

探讨长链非编码RNA-LINC01279在子宫内膜异位症(EMs)中的调控作用及分子机制。

方法

2018年9月至2019年7月,招募20例EMs患者和20例健康受试者,通过qRT-PCR检测EMs组织及正常子宫内膜中lncRNA-LINC01279的表达。采用自体移植法在Spraque-Dawley(SD)大鼠上建立EMs模型,之后测量EMs子宫内膜体积,并通过苏木精-伊红(H&E)染色观察EMs的病理形态学变化。进一步运用qRT-PCR技术检测EMs大鼠及LINC01279 shRNA转染大鼠血清中lncRNA-LINC01279和HOXA10的mRNA表达,同时采用蛋白质免疫印迹法检测HOXA10的蛋白表达。

结果

EMs患者lncRNA-LINC01279表达上调,HOXA10表达下调(p<0.01或0.001)。在线预测进一步显示lncRNA-LINC01279通过miRNA-135b调控HOXA10的表达。在EMs模型中,观察到子宫内膜显著增大,病理形态不佳,血清中lncRNA-LINC01279显著上调,miR-135b和HOXA10下调(p<0.05、0.01或0.001)。在lncRNA-LINC01279 shRNA组中,EMs大鼠经治疗后,EMs子宫内膜体积急剧减小,病理形态改善,lncRNA-LINC01279下调,miR-135b和HOXA10上调(p<0.05、0.01或0.001)。

结论

lncRNA-LINC01279通过靶向miR-135b的机制,有可能下调HOXA10的表达,因此可促进EMs的发生发展。

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