Research Paper Volume 10, Issue 11 pp 3353—3370
LOC134466 methylation promotes oncogenesis of endometrial carcinoma through LOC134466/hsa-miR-196a-5p/TAC1 axis
- 1 Department of Obstetrics and Gynecology, Huangjiahu Hospital of Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China
- 2 College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China
- 3 Department of Dermatology, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China
- 4 Department of Obstetrics and Gynecology, Hubei Provincial Hospital of TCM, Wuhan 430065, Hubei, China
- 5 Department of Oncology, The First Clinic College of Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China
- 6 Department of Oncology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430065, Hubei, China
received: August 8, 2018 ; accepted: November 4, 2018 ; published: November 28, 2018 ;https://doi.org/10.18632/aging.101644
How to Cite
Copyright: Xu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
To investigate possible mechanism of abnormal methylation of long non-coding RNA (lncRNA) on endometrial carcinoma (EC) progression, we detected the genome methylation profiling of endometrial carcinoma by bioinformatic analysis. Accordingly, gene LOC134466 was chosen for the further research. We also found that TAC1 was the target gene of LOC134466 and miRNA, hsa-miR-196a-5p, might form a connection between LOC134466 and TAC1. The relationship was further proved by dual-luciferase reporter assay. In vitro studies, DNA methylation and expression were determined by MSP and qRT-PCR respectively. Cell proliferation, apoptosis and cell cycle were demonstrated by colony formation assay, Annexin V/PI double staining and flow cytometry. Besides, the function of LOC134466 and TAC1 in EC was further confirmed by Tumor Xenograft. Our results indicated that EC progression was promoted by hypermethylated LOC134466 and TAC1. Moreover, TAC1 transcription was regulated by LOC134466 via hsa-miR-196a-5p binding. LOC134466 and TAC1 demethylation by 5-Aza-2-Deoxycytidine inhibited EC cells proliferation and accelerated cell apoptosis. Furthermore, the expression of TACR1, TACR2 and TACR3 was remarkably decreased through LOC134466 and TAC1 treatments. Our findings establish a novel regulatory axis, LOC134466/hsa-miR-196a-5p/TAC1. Downregulation of the axis promoted EC development through TACR3, which further activated neuroactive ligand-receptor interaction.