https://scholars.lib.ntu.edu.tw/handle/123456789/627414
標題: | Regulatory mechanisms and function of hypoxia-induced long noncoding RNA NDRG1-OT1 in breast cancer cells | 作者: | Chao, Hsing-Hua Luo, Jun-Liang Hsu, Ming-Hsuan Chen, Li-Han TZU-PIN LU Tsai, Mong-Hsun Chuang, Eric Y Chuang, Li-Ling LIANG-CHUAN LAI |
關鍵字: | INDUCIBLE FACTOR-1-ALPHA; COLORECTAL-CANCER; GENE-EXPRESSION; SOLID TUMORS; KAPPA-B; PROGRESSION; ALPHA; PHOSPHORYLATION; PROLIFERATION; TRANSCRIPTION | 公開日期: | 20-九月-2022 | 出版社: | SPRINGERNATURE | 卷: | 13 | 期: | 9 | 來源出版物: | Cell death & disease | 摘要: | Hypoxia is a classic feature of the tumor microenvironment that has profound effects on cancer progression and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs), a component of the noncoding genome, have been increasingly investigated due to their diverse roles in tumorigenesis. Previously, a hypoxia-induced lncRNA, NDRG1-OT1, was identified in MCF-7 breast cancer cells using next-generation sequencing. However, the regulatory mechanisms of NDRG1-OT1 remain elusive. Therefore, the purpose of this study was to investigate the regulatory mechanisms and functional roles of NDRG1-OT1 in breast cancer cells. Expression profiling of NDRG1-OT1 revealed that it was upregulated under hypoxia in different breast cancer cells. Overexpression and knockdown of HIF-1α up- and downregulated NDRG1-OT1, respectively. Luciferase reporter assays and chromatin immunoprecipitation assays validated that HIF-1α transcriptionally activated NDRG1-OT1 by binding to its promoter (-1773 to -1769 and -647 to -643 bp). Next, to investigate whether NDRG1-OT1 could function as a miRNA sponge, results of in silico analysis, expression profiling of predicted miRNAs, and RNA immunoprecipitation assays indicated that NDRG1-OT1 could act as a miRNA sponge of miR-875-3p. In vitro and in vivo functional assays showed that NDRG1-OT1 could promote tumor growth and migration. Lastly, a small peptide (66 a.a.) translated from NDRG1-OT1 was identified. In summary, our findings revealed novel regulatory mechanisms of NDRG1-OT1 by HIF-1α and upon miR-875-3p. Also, NDRG1-OT1 promoted the malignancy of breast cancer cells and encoded a small peptide. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627414 | ISSN: | 2041-4889 | DOI: | 10.1038/s41419-022-05253-2 |
顯示於: | 生理學科所 |
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