Abstract
Long non-coding RNAs (lncRNA) have been identified as key regulators of tumorigenesis and development. We aim to explore the biological functions and molecular mechanisms of lncRNA MIR200CHG in breast cancer. We found that MIR200CHG is highly expressed in breast cancer tissues and is related to the tumor size and histopathological grade. In vitro and in vivo experiments confirmed that MIR200CHG can promote breast cancer proliferation, invasion, and drug resistance. MIR200CHG directly binds to the transcription factor Y-box binding protein-1 (YB-1), and inhibits its ubiquitination and degradation. MIR200CHG regulates YB-1 phosphorylation at serine 102, thereby affecting the expression of genes related to tumor cell proliferation, apoptosis, invasion, and drug resistance. Additionally, MIR200CHG partially affects the expression of miR-200c/141-3p encoded by its intron region. Therefore, MIR200CHG can promote the proliferation, invasion, and drug resistance of breast cancer by interacting with and stabilizing YB-1, and has the potential to become a target for breast cancer treatment.
Highlights
Breast cancer is the most common malignant heterogeneous tumor in women and is the main cause of cancer deaths among women[1,2,3]
U47924.27 is annotated as homo sapiens MIR200C and MIR141 host gene (MIR200CHG; Accession number: NR_135032.1), and its intron region encodes miR-200c and miR-141. miR-200c/141 belong to the miR-200s family, which mainly regulates the expression of target genes after transcription by promoting mRNA degradation or inhibiting translation, and its functions are dependent on the tumor type and cell background[14]
In vivo and in vitro functional experiments we show that MIR200CHG enhances breast cancer proliferation, invasion, and drug resistance
Summary
Breast cancer is the most common malignant heterogeneous tumor in women and is the main cause of cancer deaths among women[1,2,3]. Studies have confirmed that long noncoding RNA (lncRNA) can be used as a tumor suppressor or oncogene to participate in the development and regulation of breast cancer, and has the potential to become a target for breast cancer detection and treatment[7,8,9]. LncRNA is defined as an RNA transcript greater than 200 nt, which has no obvious protein coding potential, but can participate in chromatin remodeling and modification, and signal transduction regulation[10]. MiR-200c/141 belong to the miR-200s family, which mainly regulates the expression of target genes after transcription by promoting mRNA degradation or inhibiting translation, and its functions are dependent on the tumor type and cell background[14]. The role of miR-200c/141 has been widely characterized, the nature of MIR200CHG is still completely unknown
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