Abstract
BackgroundOur previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear.MethodsThe luciferase reporter and ChIP assays were used to confirm the binding of LEF-1 to the putative promoter site of LINC01278 gene. The RNA immunoprecipitation and RNA pulldown were used to determine the enrichment of LINC01278 in β-catenin protein. The proteasome inhibitors (MG132) was used for detecting the β-catenin ubiquitination-proteasome degradation. Wnt/β-catenin specific agonists (LiCI), inhibitors (WiKI4) and TOP/FOP-flash reporter assay were used for detecting the activation of Wnt/β-catenin signal. Western blot was used to detected the expression of target proteins.ResultsThe online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and β-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter. Furthermore, LINC01278 negatively regulated the protein accumulation of β-catenin in the cytoplasm, into nucleus, and ultimately inhibited the transcription of downstream target genes activated by Wnt/β-catenin signal. The results of RNA immunoprecipitation and RNA pulldown proved the direct binding of LINC01278 to β-catenin protein. In addition, the combination of LINC01278 and β-catenin promotes the β-catenin ubiquitination-proteasome degradation.ConclusionIn summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 onβ-catenin signal.
Highlights
Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis
The luciferase reporter assays further showed that the luciferase activity of the TPC-1 and BCPAP cells cotransfected with LINC01278-WT and LEF-1 was significantly increased compared with the negative control (NC) group
The luciferase activity of the cells co-transfected with LEF-1 and LINC01278-mutant promoter sequence of LINC01278 (MUT) showed no significant change compared with the NC group (Fig. 1B)
Summary
Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. Thyroid cancer is the most common malignant tumor of the endocrine system [1, 2]. Lin et al Cancer Cell Int (2021) 21:380 and low mortality, the pathogenesis of PTC should be further studied. Numerous studies have shown that lncRNAs play a vital role in the occurrence and progression of cancer [10]. Our previous study showed that LINC01278 was significantly down-regulated in PTC tissues and cell lines [11]. The low expression of LINC01278 was related to tumor size, lymph node metastasis, pathological grade and clinical stage. LINC01278 inhibited the malignant proliferation and invasion of PTC cells by regulating the miR-376c-3p/DNM3 axis. The regulation mechanism of LINC01278 expression in PTC cells is still unclear
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