Open AccessLOC134466 methylation promotes oncogenesis of endometrial carcinoma through LOC134466/hsa-miR-196a-5p/TAC1 axis
Author(s) -
Hai Xu,
Yuan Sun,
Zhen Ma,
Xin Xu,
Lili Qin,
Baoping Luo
Publication year - 2018
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.101644
Subject(s) - dna methylation , methylation , cell growth , apoptosis , cancer research , chemistry , carcinogenesis , downregulation and upregulation , microbiology and biotechnology , biology , gene expression , gene , biochemistry
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.