Background and objectives: Esophageal squamous cell carcinoma (ESCC) is the most widespread type of esophageal cancer. LncRNA TUG1 was first identified in a genomic screening study for the treatment of taurine in retinal cells. This study... more
Background and objectives: Esophageal squamous cell carcinoma (ESCC) is the most widespread type of esophageal cancer. LncRNA TUG1 was first identified in a genomic screening study for the treatment of taurine in retinal cells. This study aimed at analyzing TUG1 expression in ESCC tissues collected from an Iranian population of patients. Bioinformatics study was also conducted for better understanding the function of this lnc-RNA. Methods: We examined the expression of TUG1 in 31 pairs of ESCC tissues and adjacent noncancerous tissues by qRT-PCR. Bioinformatics analysis was conducted using various databases. Student's t-test was performed using SPSS software (version 16.0) to evaluate the difference in TUG1 expression between ESCC and adjacent non-cancerous tissues. Results: TUG1 expression level in ESCC tissues was significantly higher than that in the adjacent non-cancerous tissues (P=0.04). Conclusion: TUG1 is upregulated in ESCC, which may be related to history of smoking.
designed this study. H.Z. designed and performed biology experiments. J.Q. and J.E.B designed and synthesized JQEZ5, JQEZ6 and JQEZ23.. performed all sequencing and sequencing data analysis. J.P. and J.Q. performed biochemical assays.... more
designed this study. H.Z. designed and performed biology experiments. J.Q. and J.E.B designed and synthesized JQEZ5, JQEZ6 and JQEZ23.. performed all sequencing and sequencing data analysis. J.P. and J.Q. performed biochemical assays. A.J.F. and J.Q. performed computational modeling.
Soft tissue sarcomas (STS) are a heterogenous group of rare malignancies of mesenchymal origin, affecting both children and adults. The majority of STS have a poor prognosis and advanced stage at the time of diagnosis. Standard treatments... more
Soft tissue sarcomas (STS) are a heterogenous group of rare malignancies of mesenchymal origin, affecting both children and adults. The majority of STS have a poor prognosis and advanced stage at the time of diagnosis. Standard treatments for STS largely constitute tumour resection with chemotherapy and/or radiotherapy, and there has been little significant advancement in the application of novel therapies for treatment of these tumours. The current multimodal approach to therapy often leads to long-term side effects, and for some patients, resistance to cytotoxic agents is associated with local recurrence and/or metastasis. There is, therefore, a need for novel therapeutic strategies for the treatment of STS. Recent advances in epigenetics have implicated the histone methyltransferase, EZH2, in the development and progression of diseases such as breast cancer, lymphoma and more recently STS. Here we will review the current literature for EZH2 in STS, including high expression of EZH2 in STS and correlation of this with specific features of malignancy (metastasis, histological grade, and prognosis). The effects of targeting EZH2 using RNA interference and small molecule inhibitors will also be reviewed and the potential for the use of EZH2 inhibition in therapeutic strategies for STS patients will be discussed.
Objective: Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 (PVT1) plays a critical role in the progression of non-small cell lung cancer (NSCLC), there are still many unsolved... more
Objective: Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 (PVT1) plays a critical role in the progression of non-small cell lung cancer (NSCLC), there are still many unsolved mysteries remains to be deeply elucidated. This study aimed to find a new underlying mechanism of PVT1 in regulating the tumorigenesis and development of NSCLC.
Materials And Methods: In this experimental study, Quantitative reverse transcription polymerase chain reaction (qRTPCR) was used to profile the expression of PVT1 in NSCLC tissues and cells. The effects of PVT1 on cell growth, migration and invasion were detected by colony formation assay, Matrigel-free transwell and Matrigel transwell assays, respectively. Changes of the key protein expression in Hippo and NOTCH signaling pathways, as well as epithelialmesenchymal transition (EMT) markers, were analyzed using western blot. Interaction of PVT1 with enhancer of zeste homolog 2 (EZH2) was verified by RNA pull-down, and their binding to the downstream targets was detected by Chromatin Immunoprecipitation (ChIP) assays.
Results: These results showed that PVT1 was up-regulated in NSCLC tissue and cell lines, promoting NSCLC cell proliferation, migration and invasion. Knockdown of PVT1 inhibited the expression of Yes-associated protein 1 (YAP1) and NOTCH1 signaling activation. Further, we have confirmed that PVT1 regulated expression of YAP1 through EZH2-mediated miR-497 promoter methylation resulting in the inhibition of miR-497 transcription and its target YAP1 upregulation, and finally NOTCH signaling pathway was activated, which promoted EMT and invasion and metastasis.
Conclusion: These results suggested that lncRNA PVT1 promotes NSCLC metastasis through EZH2-mediated activation of Hippo/NOTCH1 signaling pathways. This study provides a new opportunity to advance our understanding in the potential mechanism of NSCLC development.
