LncRNA TMPO‐AS1 promotes LCN2 transcriptional activity and exerts oncogenic functions in ovarian cancer
| Autor: | Guanghong Zheng, Feng Ding, Hui Zhao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Carcinogenesis E2F6 Transcription Factor Mice Nude Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Lipocalin-2 Cell Line Tumor Gene expression Genetics medicine Animals Humans Gene silencing E2F Molecular Biology Transcription factor Ovarian Neoplasms Mice Inbred BALB C Cancer Promoter medicine.disease Xenograft Model Antitumor Assays Tumor Burden Antisense RNA Gene Expression Regulation Neoplastic 030104 developmental biology Cancer research Female RNA Interference RNA Long Noncoding Ovarian cancer 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 34:11382-11394 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201902683r |
| Popis: | Ovarian cancer remains the sixth most frequently occurring cancer in women worldwide. Long noncoding RNAs (lncRNAs) are capable of regulating gene expression, and thus, participating in a wide range of biological functions and disease processes including cancer development. Our work suggests that lncRNA TMPO antisense RNA 1 (TMPO-AS1) represents an oncogenic lncRNA in ovarian cancer and presents a novel mechanism involving transcription factor E2F transcription factor 6 (E2F6) and lipocalin-2 (LCN2). We identified upregulated lncRNA TMPO-AS1 in ovarian cancer tissues and cells. siRNA-mediated silencing of lncRNA TMPO-AS1 restrained the aggressiveness of ovarian cancer cells and their pro-angiogenic ability, and reduced the expression of LCN2. LncRNA TMPO-AS1 was found to interact with E2F6, a transcriptional repressor that could bind to the promoter region of LCN2 gene. In addition, silencing of E2F6 or overexpression of LCN2 restored the aggressiveness of ovarian cancer cells and their pro-angiogenic ability following siRNA-mediated silencing of lncRNA TMPO-AS1. Taken together, we demonstrated lncRNA TMPO-AS1 could potentially promote LCN2 transcriptional activity by binding to transcription factor E2F6, and thus, stimulated the progression of ovarian cancer. These findings underscore a possible alternative therapeutic strategy for ovarian cancer treatment. |
| Databáze: | OpenAIRE |
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