Functional linc-POU3F3 is overexpressed and contributes to tumorigenesis in glioma.

Growing number of long intergenic noncoding RNAs (lincRNAs) have recently been identified in mammals as new modulators in cancer origination and progression involved in a broad range of biological processes. Long intergenic noncoding RNA POU3F3 (linc-POU3F3) has been characterized as a highly conserved functional transcription regulator in esophageal squamous cell carcinoma. The contributions of this lincRNA to glioblastoma remain unknown. In this present study, we investigated the expression pattern and functional role of linc-POU3F3 in glioma by using real-time PCR and gain-/loss-of-function studies. The results revealed that linc-POU3F3 levels were extraordinarily associated with the tumor WHO grade. In related biochemical assays, overexpression of linc-POU3F3 promotes cell viability and proliferation in glioma cells, whereas knockdown of linc-POU3F3 showed the opposite effect. As expected, we also found that linc-POU3F3 expression was negatively correlated with the mRNA level of POU3F3 (the evolutionarily conserved neighbor gene of linc-POU3F3). Our results indicate that linc-POU3F3 might affect glioma development via altering expression level of POU3F3, and lead us to believe that linc-POU3F3 may also have a crucial regulatory role in glioma progression.

Guo H ，Wu L ，Yang Q ，Ye M ，Zhu X ... -  《-》

Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells.

Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals via genome-wide sequencing studies. Many are functional, but are expressed aberrantly by cancer cells. We investigated whether levels of lincRNAs are altered during the development of esophageal squamous cell carcinoma (ESCC). We used quantitative real-time polymerase chain reaction to measure levels of 26 highly conserved lincRNAs in ESCC and surrounding nontumor tissues. A total of 182 ESCC and paired adjacent nontumor tissue samples were collected from patients undergoing tylectomy at The First Affiliate Hospital of Soochow University from 2001 through 2009; another 178 ESCC tissue pairs were collected from Guangzhou Medical University from 2002 through 2009. LincRNAs were expressed from lentiviral vectors or knocked down with small hairpin RNAs in Eca-109 and TE-1 cells. Levels of a lincRNA encoded by a gene located next to POU3F3 (linc-POU3F3) were significantly higher in ESCC than neighboring nontumor tissues. In RNA immunoprecipitation assays, linc-POU3F3 was associated with the EZH2 messenger RNA (mRNA). Overexpression of linc-POU3F3 in cell lines increased their proliferation and ability to form colonies, and reduced the expression of POU3F3 mRNA, whereas knockdown of linc-POU3F3 increased the levels of POU3F3 mRNA. CpG islands in POU3F3 were densely hypermethylated in cell lines that overexpressed linc-POU3F3; methylation at these sites was reduced by knockdown of linc-POU3F3. Pharmacologic inhibition of EZH2 increased the levels of POU3F3 mRNA and significantly reduced binding of DNA methyltransferase (DNMT)1, DNMT3A, and DNMT3B to POU3F3. ESCC cells with knockdown of linc-POU3F3 formed xenograft tumors more slowly in mice than control ESCC cells. Levels of linc-POU3F3 are increased in ESCC samples from patients compared with nontumor tissues. This noncoding RNA contributes to the development of ESCC by interacting with EZH2 to promote methylation of POU3F3, which encodes a transcription factor.

Li W ，Zheng J ，Deng J ，You Y ，Wu H ，Li N ，Lu J ，Zhou Y ... -  《-》

Knockdown of linc-POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer.

Shan TD ，Xu JH ，Yu T ，Li JY ，Zhao LN ，Ouyang H ，Luo S ，Lu XJ ，Huang CZ ，Lan QS ，Zhong W ，Chen QK ... -  《Oncotarget》

Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients.

Li Y ，Li Y ，Wang D ，Meng Q ... -  《-》

Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3.

Lang HL ，Hu GW ，Chen Y ，Liu Y ，Tu W ，Lu YM ，Wu L ，Xu GH ... -  《-》