CTCF-Induced lncRNA C5orf66-AS1 Facilitates the Progression of Triple-Negative Breast Cancer via Sponging miR-149-5p to Up-Regulate CTCF and CTNNB1 to Activate Wnt/β-Catenin Pathway
- 1 June 2022
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 42 (6), e0018821
- https://doi.org/10.1128/mcb.00188-21
Abstract
Triple-negative breast cancer (TNBC) represents one of the subtypes of breast cancer with high aggressiveness. Long noncoding RNAs (lncRNAs) are well-known to function as crucial regulators in human cancers which include TNBC. Triple-negative breast cancer (TNBC) represents one of the subtypes of breast cancer with high aggressiveness. Long noncoding RNAs (lncRNAs) are well-known to function as crucial regulators in human cancers which include TNBC. Nevertheless, the specific role of the lncRNA C5orf66-AS1 in TNBC is unclear. In this study, we tested C5orf66-AS1 expression in TNBC cells using quantitative real-time PCR (qRT-PCR) and used functional assays to detect cell behaviors, which showed that C5orf66-AS1 was highly expressed in TNBC cells and that C5orf66-AS1 knockdown attenuated cell proliferation, migration, and invasion while promoting cell apoptosis. Through a luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and chromatin immunoprecipitation (ChIP) assay, we identified the binding capacity of C5orf66-AS1 to RNAs. Furthermore, miR-149-5p was proven to be sponged by C5orf66-AS1. CCCTC-binding factor (CTCF) was confirmed as the target of miR-149-5p and could transcriptionally activate C5orf66-AS1 expression in TNBC cells. We also discovered that C5orf66-AS1 activated the Wnt/beta-catenin signaling pathway by upregulating catenin beta 1 (CTNNB1). Importantly, CTNNB1 could be targeted by miR-149-5p. In rescue assays, it was proven that overexpressing CTCF and CTNNB1 or inhibiting miR-149-5p could totally reverse the inhibitory effect of silencing C5orf66-AS1 on TNBC progression. In short, the lncRNA C5orf66-AS1 acted as an oncogene to facilitate TNBC malignancy.Keywords
Funding Information
- Science and Technology Project of Lianyungang Municipal Health Commission (Grant No. 202020)
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