The Wnt/β-Catenin/LEF1 Pathway Promotes Cell Proliferation at Least in Part Through Direct Upregulation of miR-17-92 Cluster

Abstract

The miR-17-92 cluster is involved in animal development and homeostasis, and its dysregulation leads to human diseases such as cancer. In the present study, we investigated the functional link between miR-17-92 cluster and Wnt/β-catenin signaling pathway in ICP2 and DF1 cells. We demonstrated that ectopic expression of either LEF1 or β-catenin increased the promoter activity of the miR-17-92 cluster host gene (MIR17HG) and combined ectopic expression of LEF1 and β-catenin further enhanced the promoter activity; while knockdown of either LEF1 or β-catenin reduced the MIR17HG promoter activity. Both LEF1 and β-catenin could directly bind to the MIR17HG promoter. Furthermore, we demonstrated that low doses of lithium chloride (LiCl), an activator of Wnt/β-catenin signaling pathway, increased MIR17HG promoter activity and the endogenous expression of the miR-17-92 cluster, while high doses of LiCl had the opposite effects. Treatment with XAV-939, an inactivator of the Wnt/β-catenin pathway, reduced the endogenous expression of miR-17-92 cluster. Finally, we found that low doses of LiCl promoted the proliferation of ICP2 and DF1 cells, while high doses of LiCl inhibited the proliferation of ICP2 and DF1 cells. Taken together, our results reveal that MIR17HG is a target of LEF1 and the Wnt/β-catenin pathway and suggest that the miR-17-92 cluster may, at least in part, mediate the proliferation-promoting effect of the Wnt/β-catenin pathway in cell proliferation.

Long non‐coding RNA LEF1‐AS1 is involved in the progression of retinoblastoma through regulating the Wnt/β‐catenin pathway

“…The β‐catenin and LEF1 have been confirmed to function as key downstream effectors in the Wnt signalling pathway . To explore the molecular mechanism of LEF1‐AS1 in retinoblastoma, we conducted western blots to determine the effect of LEF1‐AS1 on β‐catenin and LEF1 expression.…”

“…Meanwhile, we explored the molecular mechanism of LEF1‐AS1 in retinoblastoma. LEF1‐AS1 has been suggested to interact with LEF1 to regulate tumour cell proliferation and mobility, and LEF1 is a key regulatory factor of the Wnt signalling pathway . Therefore, we estimated the effect of LEF1‐AS1 on β‐catenin and LEF1 expression and found that silencing LEF1‐AS1 expression dramatically impaired β‐catenin and LEF1 expression in retinoblastoma cells.…”

“…The β-catenin and LEF1 have been confirmed to function as key downstream effectors in the Wnt signalling pathway. [24][25][26] To explore the molecular mechanism of LEF1-AS1 in retinoblastoma, we conducted western blots to determine the effect of LEF1-AS1 on β-catenin and LEF1 expression. We found that silencing LEF1-AS1 expression dramatically impaired β-catenin and LEF1 expression in SO-Rb50 and HXO-RB44 cells ( Figure 5).…”

“…LEF1-AS1 has been suggested to interact with LEF1 to regulate tumour cell proliferation and mobility, 13,20,22 and LEF1 is a key regulatory factor of the Wnt signalling pathway. [24][25][26] Therefore, we estimated the effect of LEF1-AS1 on β-catenin and LEF1 expression and found that silencing LEF1-AS1 expression dramatically impaired β-catenin and LEF1 expression in retinoblastoma cells. We preliminarily hypothesized that silencing LEF1-AS1 inhibited retinoblastoma cell proliferation, migration, and invasion through the Wnt signalling pathway.…”

Identification of Long Non-coding RNAs Expressed During Early Adipogenesis

“…Hotairm1 was found to be downregulated in hepatocellular carcinoma and inhibited the proliferation and promote the apoptosis by suppressing the Wnt/-catenin signaling pathway and then inhibit the tumor progression. (Mu et al, 2019;Zhang et al, 2018) Yuan et al found that the overexpression of interferon regulatory factor-1 (IRF-1) downregulated Mir17hg in gastric cancer cells and inhibited the tumor progression by inhibiting Wnt/-catenin signaling pathway. Yuan et al (2019) Wincr1 was found to be activated by Wnt/-catenin signaling pathway in fibroblast cells.…”