Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2.

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies. The unfavourable prognosis is mainly due to the lack of early-stage diagnosis, drug resistance and recurrence. Therefore, it needs to investigate the mechanism of OC tumorigenesis and identify effective biomarkers for the clinical diagnosis. It is reported that long noncoding RNAs (lncRNAs) play important roles during the tumorigenesis of OC. Therefore, the present study aimed to study the role and clinical significance of LncRNAs ATB (lnc-ATB) in the development and progression of OC. In our research, lnc-ATB expression in OC tissues was elevated compared with adjacent normal tissues and high expression of lnc-ATB was associated with poor outcomes of OC patients. The silencing of lnc-ATB blocked cell proliferation, invasion and migration in SKOV3 and A2780 cells. RNA immunoprecipitation and RNA pull-down results showed that lnc-ATB positively regulated the expression of EZH2 via directly interacting with EZH2. Besides, the overexpression of EZH2 partly rescued lnc-ATB silencing-inducing inhibition of cell proliferation, invasion and migration. Chromatin immunoprecipitation assay results demonstrated that the silencing of lnc-ATB reduced the occupancy of caudal-related homeobox protein 1, Forkhead box C1, Large tumour suppressor kinase 2, cadherin-1 and disabled homolog 2 interacting protein promoters on EZH2 and H3K27me3. These data revealed the oncogenic of lnc-ATB and provided a novel biomarker for OC diagnosis. Furthermore, these findings indicated the mechanism of lnc-ATB functioning in the progression of OC, which provided a new target for OC therapy.

Chen XJ ，An N 《-》

Long non-coding RNA SNGH7 Is activated by SP1 and exerts oncogenic properties by interacting with EZH2 in ovarian cancer.

Long non-coding RNAs (lncRNAs) are key regulators or a range of diseases and chronic conditions such as cancers, but how they function in the context of ovarian cancer (OC) is poorly understood. The Coding-Potential Assessment Tool was used to assess the likely protein-coding potential of SNHG7. SNHG7 expression was elevated in ovarian tumour tissues measured by qRT-PCR. The online database JASPAR was used to predict the transcription factors binding to SNHG7. Twenty-four-well Transwell plates were used for invasion assays. RNA immunoprecipitation was performed to determine RNA-protein associations. EdU assay was introduced to detect cell proliferation. Chromatin immunoprecipitation was performed to confirm the directly interaction between DNA and protein. We discovered that in the context of OC there is a significant up-regulation of the lncRNA SNHG7. Knocking down this lncRNA disrupted both OC cell invasion and proliferation, while its overexpression had the opposite effect. SP1 binding sites were present in the SNHG7 promoter, and chromatin immunoprecipitation (ChIP) confirmed direct SP1 binding to this region, activating SNHG7 transcription. We found that at a mechanistic level in OC cells, KLF2 is a probable SNHG7 target, as we found that SHNCCC16 directly interacts with EZH2 and thus represses KLF2 expression. In summary, this research demonstrates that lncRNA SNHG7 is an SP1-activated molecule that contributes to OC progression by providing a scaffold whereby EZH2 can repress KLF2 expression.

Bai Z ，Wu Y ，Bai S ，Yan Y ，Kang H ，Ma W ，Zhang J ，Gao Y ，Hui B ，Ma H ，Li R ，Zhang X ，Ren J ... -  《-》

LINC01210 accelerates proliferation, invasion and migration in ovarian cancer through epigenetically downregulating KLF4.

In recent years, a large number of studies have shown that differentially expressed lncRNAs in tumors are capable of inducing tumorigenesis and promoting tumor development. However, the role of LINC01210 in OC still remains unclear. Relative levels of LINC01210 and KLF4 in OC tissues containing in the GSE40595 dataset and those collected in our hospital were determined. Prognostic potential of LINC01210 in OC was evaluated by Kaplan-Meier method. Correlation between expression levels of LINC01210 and KLF4 was assessed by Spearman correlation test. After silence of LINC01210 in A2780 and HO8910 cells, changes in proliferative, migratory and invasive abilities were examined. Moreover, the interaction between LINC01210 and KLF4 was explored by RIP and ChIP. Rescue experiments were conducted to uncover the involvement of KLF4 in LINC01210-regulated OC progression. LINC01210 was upregulated in OC tissues and KLF4 was downregulated. LINC01210 level was higher in OC patients with metastases or advanced stage. Besides, its level was negatively correlated to DFS (disease-free survival) and OS (overall survival) of OC patients. Silence of LINC01210 attenuated proliferative, migratory and invasive abilities in A2780 and HO8910 cells. Through analyzing the GSE40595 dataset, LINC01210 was found to be negatively linked to KLF4. RIP assay further verified the interaction between LINC01210 and KLF4. Knockdown of LINC01210 markedly decreased the recruitment ability of EZH2 to KLF4. Importantly, silence of KLF4 could reverse regulatory effects of LINC01210 on cellular behaviors of OC. LINC01210 is upregulated in OC and predicts a poor prognosis. It accelerates proliferation, invasion and migration in OC cells through epigenetically downregulating KLF4.

Zhang C ，Liu J ，Zhang Y ，Luo C ，Zhu T ，Zhang R ，Yao R ... -  《-》

The long non-coding RNA SNHG1 promotes bladder cancer progression by interacting with miR-143-3p and EZH2.

The long non-coding RNA (lncRNA) SNHG1 has been shown to be implicated in the progression of multiple human carcinomas. Nevertheless, the biological functions and potential mechanism of SNHG1 in bladder cancer (BC) are uncharacterized. In the present study, SNHG1 was found to be substantially up-regulated in BC tissues and cells and was intimately correlated with the TNM stage, lymphatic invasion, metastasis and recurrence-free survival in BC patients. Down-regulation of SNHG1 dramatically attenuated the proliferation, migration and invasion of BC cells, whereas the ectopic overexpression of SNHG1 had the opposite effects in vitro. The in vivo experimental results also indicated that SNHG1 down-regulation hampered the tumour growth and metastasis of BC cells. Mechanistic investigations revealed that SNHG1 enhances HK2 expression by serving as an endogenous sponge to regulate miR-143-3p in the cytoplasm of BC cells. In the nucleus, SNHG1 could interact with EZH2 and regulate the histone methylation of the CDH1 promoter, altering the biological behaviours of BC cells. Overall, these findings elucidate an oncologic role of SNHG1 in BC and provide a new therapeutic strategy against BC.

Xiang W ，Lyu L ，Huang T ，Zheng F ，Yuan J ，Zhang C ，Jiang G ... -  《-》

LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma.

Zhang J ，Li WY ，Yang Y ，Yan LZ ，Zhang SY ，He J ，Wang JX ... -  《-》