Long non-coding RNA VCAN-AS1 promotes the malignant behaviors of breast cancer by regulating the miR-106a-5p-mediated STAT3/HIF-1α pathway
Autor: | Peng Du, Qi Xiao, Xingjian Zhang, Yong Li, Guoyong Li, Kaifeng Luo, Jisheng Zhu |
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Rok vydání: | 2021 |
Předmět: |
STAT3 Transcription Factor
Untranslated region Breast Neoplasms Bioengineering cerna Biology Applied Microbiology and Biotechnology stat3 breast cancer Cell Line Tumor medicine Humans Breast STAT3 Competing endogenous RNA Cell growth Cancer RNA General Medicine Middle Aged Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Long non-coding RNA MicroRNAs hif-1α STAT protein Cancer research biology.protein Female RNA Long Noncoding vcan-as1 mir-106a-5p TP248.13-248.65 Signal Transduction Research Article Research Paper Biotechnology |
Zdroj: | Bioengineered, Vol 12, Iss 1, Pp 5028-5044 (2021) Bioengineered article-version (VoR) Version of Record |
ISSN: | 2165-5987 2165-5979 |
Popis: | An accumulating number of studies have found that long noncoding RNAs (lncRNAs) participate in breast cancer (BC) development. LncRNA VCAN-AS1, a novel lncRNA, has been confirmed to regulate the progression of gastric cancer, while its role in BC is elusive. Here, our results illustrate that VCAN-AS1 is overexpressed in BC tissues and cells, while miR-106a-5p was downregulated and negatively correlated with VCAN-AS1. In addition, high VCAN-AS1 expression and low miR-106a-5p expression were closely correlated with poor overall survival in BC patients. Functional experiments confirmed that VCAN-AS1 overexpression notably accelerated BC cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) and enhanced tumor cell growth while also suppressing cell apoptosis. However, overexpression of miR-106a-5p had the opposite effects. In addition, rescue experiments confirmed that overexpression of VCAN-AS1 inhibited the tumor-suppressive effects mediated by miR-106a-5p. Mechanistically, through bioinformatics analysis, we found that VCAN-AS1 functions as a competitive endogenous RNA (ceRNA) of miR-106a-5p, which targets the 3ʹ untranslated region (UTR) of signal transducer and activator of transcription 3 (STAT3). Further experiments indicated that miR-106a-5p downregulated the STAT3/hypoxia-inducible factor-1alpha (HIF-1α) pathway, while activating the STAT3 pathway reversed miR-106a-5p-mediated antitumor effects. Collectively, our data suggest that VCAN-AS1 is upregulated in breast cancer and promotes its progression by regulating the miR-106a-5p-mediated STAT3/HIF-1α pathway. This study provides a new target for BC therapy. |
Databáze: | OpenAIRE |
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