lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation, metastasis and epithelial-mesenchymal transition in bladder cancer.

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.

Qiu F ，Zhang MR ，Zhou Z ，Pu JX ，Zhao XJ ... -  《-》

Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer.

Liu YY ，Chen ZH ，Peng JJ ，Wu JL ，Yuan YJ ，Zhai ET ，Cai SR ，He YL ，Song W ... -  《Scientific Reports》

LncROR Promotes Bladder Cancer Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition.

LncRNA ROR, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, the molecular biological function in bladder cancer has not been clearly elucidated. The aim of this study is to explore ROR expression levels and evaluated its function in bladder cancer. LncRNA ROR expression levels in the 36 pairs of bladder cancer tissues (and corresponding non-tumor tissues) and bladder cancer cells were assessed by qRT-PCR. MTT assay, colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays, attachment/detachment and western blotting were performed to assess the effects of ROR on proliferation, apoptosis, migration/invasion and epithelial-to-mesenchymal (EMT) phenotypes in BC cells in vitro. ZEB1 is target of ROR. Rescue assays were performed to further confirm that ROR contributes to the progression of BC cells through targeting ZEB1. LncRNA ROR was up-regulated in bladder cancer tissues (compared to adjacent non-tumor tissues) and was almost overexpression in bladder cancer cells (compared with normal urothelial cell line SVHUC-1 cells). Increased lncRNA ROR expression significantly promoted tumor cells proliferation, inhibited cells apoptosis, facilitated cells metastasis and contributed to the formation of EMT phenotype. While down-regulated ROR could obviously inhibit cells proliferation, promote cells apoptosis, inhibit metastasis and reverse EMT to MET. ZEB1 was a target gene of ROR and was positive correlation with the level of ROR in cancer tissues. These results indicated that lncRNA ROR was associated with tumor progression in bladder cancer cells.

Chen Y ，Peng Y ，Xu Z ，Ge B ，Xiang X ，Zhang T ，Gao L ，Shi H ，Wang C ，Huang J ... -  《-》

Long non-coding RNA GHET1 promotes human breast cancer cell proliferation, invasion and migration via affecting epithelial mesenchymal transition.

Song R ，Zhang J ，Huang J ，Hai T ... -  《-》

Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo.

Recently, increasing evidences indicated that Platycodin D (PD) served as an effective anti-tumor drug for cancer treatment in clinic. However, the molecular mechanisms are still unclear. In the present study, we proved that PD regulated LncRNA-XIST/miR-335 axis to hamper the development of bladder cancer in vitro and in vivo. Mechanistically, PD inhibited malignant phenotypes, including cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in bladder cancer cells in a time- and dose-dependent manner. In addition, the following experiments validated that PD inhibited LncRNA-XIST expressions, while increased miR-335 expression levels in bladder cancer cells. Next, by conducting the dual-luciferase reporter gene system assay and RNA pull-down assay, we validated that LncRNA-XIST inhibited miR-335 expressions through acting as RNA sponges, and the promoting effects of PD stimulation on miR-335 levels were abrogated by upregulating LncRNA-XIST. Interestingly, both silencing LncRNA-XIST and miR-335 overexpression enhanced the inhibiting effects of PD on the malignant phenotypes in bladder cancer cells. Consistently, the xenograft tumor-bearing mice models were established, and the data indicated that PD slowed down tumor growth and inhibited tumorigenesis in vivo, which were also aggravated by downregulating LncRNA-XIST. In general, analysis of data proved that targeting LncRNA-XIST/miR-335 axis was novel to enhance the anti-tumor effects of PD in bladder cancer in vitro and in vivo, and this study provided alternative therapeutic strategies for bladder cancer treatment in clinic.

Chen D ，Chen T ，Guo Y ，Wang C ，Dong L ，Lu C ... -  《-》