<p>LncRNA PVT1 Regulates TRPS1 Expression in Breast Cancer by Sponging miR-543</p>

Abstract

Background Breast cancer is the most common female malignancy with high invasion and metastasis abilities. Studies have shown that long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is an oncogene and is positively correlated with progression and metastasis of breast tumors. However, the detailed mechanism of PVT1 in breast cancer tumorigenesis is not fully understood. Methods Real-time polymerase quantitative chain reaction (RT-qPCR) was performed to identify the expression levels of PVT1, miR-543 and trichorhinophalangeal syndrome-1 gene (TRPS1) in breast cancer tissues and cells. Cell proliferation was measured by plate clone formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. Apoptosis and motility of MCF-7 and MDA-MB-436 cells were assessed with flow cytometry assay and transwell migration and invasion analyses, respectively. In addition, a model was established to probe the function of PVT1 silencing in vivo. The target relationship among PVT1, miR-543 or TRPS1 was confirmed by dual-luciferase reporter analysis, RNA immunoprecipitation (RIP) and RNA pull down assays. The protein expression level of TRPS1 was evaluated with Western blot assay. Results PVT1 expression was upregulated in breast cancer tissues and cell lines. In addition, PVT1 silencing inhibited breast cancer cell growth and motility, while increased apoptosis. Meanwhile, the effects of PVT1 or miR-543 could be reversed by introducing overexpressed plasmid of miR-543 or TRPS1 in breast cancer cell lines, respectively. Conclusion Knockdown of PVT1 repressed breast cancer cell growth and motility, and induced apoptosis in vitro and reduced tumor volume and weight in vivo. Mechanically, the overexpression of PVT1 enhanced TRPS1 level by negatively targeted miR-543 in breast cancer.

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

“…Multiple mechanisms have been described in order to understand PVT1 ’s role in breast tumorigenesis. PVT1 suppression enhanced TRPS1 levels by negatively targeting miR-543 in BC [ 238 ]. PVT1 binds KLF5, an interaction that is enhanced by BAP1 (BRCA1-associated protein), to upregulate beta-catenin signaling and promote TNBC tumorigenesis [ 237 ].…”

miR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T)

“…By intersecting the miRNA list of GSE113740 (selection criteria: adjusted P < 0.05, |logFC|≥1) and that of GSE146477 (selection criteria: adjusted P < 0.05, |log 2 FC|≥1), miR-543 was identified as the candidate miRNA that may participate in breast cancer pathogenesis ( Figure 1a ). miR-543 was a significant suppressor of breast cancer [ 6 , 24 , 25 ]. Nonetheless, the study of miR-543 in breast cancer is still limited.…”

Long Non-Coding RNAs as Potential Diagnostic and Prognostic Biomarkers in Breast Cancer: Progress and Prospects

“…Several studies have shown the connection between PVT1 and different miRNAs in breast cancer. PVT1 functions as a sponge to regulate miR-543 ( 111 ), which is a known tumor suppressor miRNA in breast cancer ( 112 ). The tumorigenic potency of PVT1 could be abrogated by miR-543 overexpression, and loss of PVT1 is associated with inhibition of growth, increased apoptosis, and decreased tumor size ( 111 ).…”

“…PVT1 functions as a sponge to regulate miR-543 ( 111 ), which is a known tumor suppressor miRNA in breast cancer ( 112 ). The tumorigenic potency of PVT1 could be abrogated by miR-543 overexpression, and loss of PVT1 is associated with inhibition of growth, increased apoptosis, and decreased tumor size ( 111 ). A cluster of oncogenes (miR-1204, 1205, 1206, 1207-3p, 1207-5p, 1208) at the 8q24.21 locus is regulated by PVT1 ( 193 ).…”