10.6084/m9.figshare.7960730.v1
Zhangzhao Gao
Zhangzhao
Gao
Mengjiao Chen
Mengjiao
Chen
Xueke Tian
Xueke
Tian
Lu Chen
Lu
Chen
Le Chen
Le
Chen
Xiaoli Zheng
Xiaoli
Zheng
Hua Wang
Hua
Wang
Jinchao Chen
Jinchao
Chen
An Zhao
An
Zhao
Qingqing Yao
Qingqing
Yao
Qianying Zhu
Qianying
Zhu
Shengnan Jin
Shengnan
Jin
Haihong Hu
Haihong
Hu
Su Zeng
Su
Zeng
Lushan Yu
Lushan
Yu
A novel human lncRNA SANT1 <i>cis</i>-regulates the expression of <i>SLC47A2</i> by altering SFPQ/E2F1/HDAC1 binding to the promoter region in renal cell carcinoma
Taylor & Francis Group
2019
SANT1
SLC47A2
lncRNA
renal cell carcinoma
epigenetics
2019-04-05 18:15:40
Journal contribution
https://tandf.figshare.com/articles/journal_contribution/A_novel_human_lncRNA_SANT1_i_cis_i_-regulates_the_expression_of_i_SLC47A2_i_by_altering_SFPQ_E2F1_HDAC1_binding_to_the_promoter_region_in_renal_cell_carcinoma/7960730
<p><i>SLC47A2</i> encodes MATE 2-K in the kidney, which mediates the secretion of certain endogenous and exogenous compounds. <i>SLC47A2</i> was dramatically repressed in patients with renal cell carcinoma (RCC), and a lower level of <i>SLC47A2</i> might act as a negative prognostic marker, although the mechanism is not well understood. In this study, we aimed to investigate the mechanism <i>via</i> which <i>SLC47A2</i> is downregulated in RCC. Based on the annotation information of the <i>SLC47A2</i> locus available in the UCSC genome browser database, we identified a novel lncRNA, which is transcribed from the <i>SLC47A2</i> locus and named it SANT1. Overexpression and knock-down assays were performed to investigate the effects of SANT1 on <i>cis</i>-regulation of <i>SLC47A2</i>. We verified the direct binding between SANT1 and SFPQ/E2F1/HDAC1 using the cross-linking and immunoprecipitation (CLIP) assay. Chromatin immunoprecipitation was performed to confirm the molecular mechanism <i>via</i> which SANT1 activates the transcription of the <i>SLC47A2</i> coding region. We observed that SANT1 can <i>cis</i>-regulate its own genetic locus. In tumour-adjacent tissues, the <i>SLC47A2</i> locus highly expresses SANT1, which can remove the regulatory SFPQ/E2F1/HDAC1 suppressor complex from the promoter region, thereby significantly increasing the levels of the H3K27ac modification and RNAPII binding. Owing to a low SANT1 level, the binding of this inhibitory complex in the promoter region is upregulated in RCC, which results in silencing of the <i>SLC47A2</i> coding region. In conclusion, we identified a novel lncRNA and elucidated the mechanism <i>via</i> which it regulates <i>SLC47A2</i> expression in RCC.</p>