LncRNA DLG5-AS1 facilitates breast cancer cell proliferation and invasion by promoting EZH2-mediated transcriptional silencing of SFRP1.

Rapid proliferation and metastasis of breast cancer contributed to poor clinical prognosis. Accumulating evidence revealed that the dysregulation of long noncoding RNAs (lncRNAs) was associated with breast cancer progression. However, the role of lncRNA DLG5-AS1 in breast cancer has not been established. Here, we investigated the mechanisms of DLG5-AS1 in the development of breast cancer. We found that the expression of DLG5-AS1 was significantly upregulated in breast cancer tissues and cell lines. DLG5-AS1 interference markedly restrained AU565 cell proliferation, invasion, the expression of apoptosis related (caspase3 and caspase8) and Wnt/β-catenin pathway related proteins (wnt5a, β-Catenin and c-Myc), as well as promoted cell apoptosis, whereas DLG5-AS1 overexpression showed an opposite effects. In addition, DLG5-AS1 could directly bind with miR-519 b-3p. We also found that enhancer of zeste homolog 2 (EZH2) is a direct target of miR-519 b-3p, and DLG5-AS1 upregulated EZH2 expression by inhibiting the expression of miR-519 b-3p. EZH2 restrained secreted frizzled related protein 1 (SFRP1) expression through inducing H3 histone methylation in its promoter. MiR-519 b-3p overexpression or SFRP1 knockdown memorably reversed the effects of DLG5-AS1 overexpression on cell functions and Wnt/β-Catenin pathway related protein expression. Finally, in vivo experiments demonstrated that silencing of DLG5-AS1 inhibited xenograft tumor development in mice. Taken together, these findings demonstrated that DLG5-AS1 facilitated cell proliferation and invasion by promoting EZH2-mediated transcriptional silencing of SFRP1 in breast cancer.

Cai Y ，Liu Y ，Sun Y ，Ren Y ... -  《-》

In vivo and in vitro effects of microRNA-27a on proliferation, migration and invasion of breast cancer cells through targeting of SFRP1 gene via Wnt/β-catenin signaling pathway.

Kong LY ，Xue M ，Zhang QC ，Su CF ... -  《Oncotarget》

Silencing microRNA-27a inhibits proliferation and invasion of human osteosarcoma cells through the SFRP1-dependent Wnt/β-catenin signaling pathway.

Osteosarcoma is the most common malignant tumor of bone with a high potential for metastasis. Importantly, microRNA-27a (miR-27a) is involved in the progression of osteosarcoma. The present study aims to discuss the effects of miR-27a and its target gene secreted frizzled related protein 1 (SFRP1) on proliferation and invasion of human osteosarcoma cells via Wnt/β-catenin signaling pathway. The expression of miR-27a and SFRP1 in osteosarcoma tissues and cells was detected, followed by identification of their relations. Subsequently, miR-27a mimic, miR-27a inhibitor, or siRNA against SFRP1 were introduced into cells (HOS and U2OS) to investigate their role in cell proliferation and invasion. The expression of Wnt/β-catenin signaling pathway-related gene was analyzed to further uncover the regulatory mechanism of miR-27a. The osteosarcoma tissues and cells exhibited elevated miR-27 expression and reduced SFRP1 expression. SFRP1 was verified to be a target gene of miR-27a. Meanwhile, silenced miR-27a inhibited proliferation and invasion of human osteosarcoma cells. Finally, silencing miR-27a inhibited the activation of Wnt/β-catenin signaling pathway, evidenced by reduced β-catenin expression. Our study draws a conclusion that silencing miR-27a dampens osteosarcoma progression, which might be achieved through the inactivation of the Wnt/β-catenin signaling pathway by up-regulating SFRP1.

Mu Y ，Zhang L ，Chen X ，Chen S ，Shi Y ，Li J ... -  《-》

LncRNA LEF1-AS1 silencing diminishes EZH2 expression to delay hepatocellular carcinoma development by impairing CEBPB-interaction with CDCA7.

Gao J ，Dai C ，Yu X ，Yin XB ，Zhou F ... -  《-》

SOX9-activated PXN-AS1 promotes the tumorigenesis of glioblastoma by EZH2-mediated methylation of DKK1.

Increasing evidence has validated the essential regulation of long non-coding RNAs (lncRNAs) in the biological process of tumours. LncRNA PXN-AS1 has been discovered to be as a tumour suppressor in pancreatic cancer; however, its function and mechanism remain greatly unknown in glioblastoma (GBM). Our present study indicated that PXN-AS1 was highly expressed in GBM tissues and cells. Besides, the knock-down of PXN-AS1 was closely associated with the inhibitory proliferation and inducing apoptosis of GBM cells. PXN-AS1 inhibition was also found to restrain GBM tumour growth. Importantly, SOX9 functioned as a transcription factor and activated PXN-AS1 expression, and overexpressed PXN-AS1 rescued the inhibitory role of down-regulated SOX9 in GBM cell growth. Subsequently, it was discovered that PXN-AS1 activated Wnt/β-catenin pathway. DKK1 was widely known as an inhibitor gene of Wnt/β-catenin pathway, and its expression was negatively associated with PXN-AS1 and SOX9. Interestingly, we found that PXN-AS1 could recruit EZH2 to mediate the H3K27me3 level of DKK1 promoter. Restoration experiments manifested that DKK1 knock-down counteracted PXN-AS1 depletion-mediated repression in GBM cell growth. All facts pointed out that PXN-AS1 might be of importance in exploring the therapeutic strategies of GBM.

Chen H ，Hou G ，Yang J ，Chen W ，Guo L ，Mao Q ，Ge J ，Zhang X ... -  《-》