BackgroundThe long non-coding RNA x-inactivespecifictranscript (xIST) plays a crucial role in transcriptional silencing of the x chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor invo...
详细信息
BackgroundThe long non-coding RNA x-inactivespecifictranscript (xIST) plays a crucial role in transcriptional silencing of the x chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-mesenchymal transition (EMT) *** study aimed to investigate the impact of xIST on esophageal squamous cell carcinoma (ESCC) progression and its underlying mechanism involving the miR-34a/ZEB1/E-cadherin/EMT *** and ZEB1 expression were analyzed using quantitative PCR and immunohistochemistry. xIST knockdown was achieved in KYSE150 ESCC cells using siRNA or shRNA lentivirus transfection. Proliferation, migration, and invasion abilities were assessed, and luciferase reporter assays were performed to confirm xIST-miR-34a-ZEB1 interactions. In vivo ESCC growth was evaluated using a xenograft mouse *** and ZEB1 were upregulated in tumor tissues, correlating with metastasis and reduced survival. xIST knockdown inhibited proliferation, migration, and invasion of KYSE150 cells. It decreased ZEB1 expression, increased E-cadherin and miR-34a levels. Luciferase reporter assays confirmed miR-34a binding to xIST and ZEB1. xIST knockdown suppressed xenograft tumor *** promotes ESCC progression via the miR-34a/ZEB1/E-cadherin/EMT pathway. Targeting the xIST/miR-34a/ZEB1 axis holds therapeutic potential and serves as a prognostic biomarker in *** AbstractThis study has discovered an xIST-associated pathway involved in the regulation of ZEB1 expression, thereby influencing the progression of squamous cell carcinoma (ESCC). The specific mechanism is as follows: xIST can regulates ZEB1 expression by sponging miR-34a, ultimately promoting the metastasis of tumor by down-regulating the expression of E-cadherin.
x chromosome inactivation in mammals was first described over 30 years ago. The biological problem is how to achieve gene dosage equivalence between xx females and xY males;the solution is to genetically silence one w...
详细信息
x chromosome inactivation in mammals was first described over 30 years ago. The biological problem is how to achieve gene dosage equivalence between xx females and xY males;the solution is to genetically silence one whole x chromosome in each cell of the early developing female embryo. The molecular mechanism by which this is achieved, however, remains a mystery. Recently, through the discovery of the xist gene, it appears that we may be on the brink of learning how this unique phenomenon is mediated. Here, I discuss the developmental regulation of x inactivation and the candidacy of xist as the x chromosome inactivation centre, with particular reference to its possible role in the initiation, spread and maintenance of x inactivation.
Long non-coding RNA (lncRNA) is an important member of non-coding RNA family and emerging evidence has indicated that it plays a pivotal role in many physiological and pathological processes. The IncRNA xinactive spe...
详细信息
Long non-coding RNA (lncRNA) is an important member of non-coding RNA family and emerging evidence has indicated that it plays a pivotal role in many physiological and pathological processes. The IncRNA x inactive specific transcript (xIST) is a potential tumour suppressor in some types of cancers. However, the expression and function of xIST in breast cancer remain largely unclear. The objective of this study was to evaluate the expression and biological role of xIST in breast cancer. The results showed that xIST was significantly down-regulated in breast cancer tissues and cell lines. Further functional analysis indicated that overexpression of xIST remarkably inhibited breast cancer cell growth, migration, and invasion. The results of luciferase reporter assays verified that miR-155 was a direct target of xIST in breast cancer. Moreover, caudal-type homeobox 1 (CDx1) was identified as a direct target of miR-155 and miR-155/CDx1 rescued the effects of xIST in breast cancer cells. Taken together, our results suggest that xIST is down-regulated in breast cancer and suppresses breast cancer cell growth, migration, and invasion via the miR-155/CDx1 axis. (C) 2018 Published by Elsevier Inc.
Objective: Esophageal cancer is one of the deadliest cancers worldwide occurring at upper gastrointestinal tract. This study aimed to explore the possible role of long non-coding RNA x inactive specific transcript (xI...
详细信息
Objective: Esophageal cancer is one of the deadliest cancers worldwide occurring at upper gastrointestinal tract. This study aimed to explore the possible role of long non-coding RNA x inactive specific transcript (xIST) in the development of esophageal cancer. Material and methods: The lncRNA xIST expressions both in esophageal cancer tissues and in cells were investigated. The TE-1 and SKGT-4 cells were transfected with LV-sh-xIST and LV-scramble for the further detection of the effects of xIST expression on cell biological processes, including proliferation, apoptosis and the expression of apoptosis-related proteins, migration, invasion and the expression of epithelial-mesenchymal transition markers. Additionally, the regulatory relationships between lncRNA xIST and miR-494, between miR494 and CDK6, between miR-494/CDK6 and JAK2/STAT3 pathway were investigated. Results: LncRNA xIST was overespressed in esophageal cancer tissues and cells. Suppression of xIST significantly inhibited the proliferation, migration and invasion, but induced apoptosis of two kinds of cells, TE-1 and SKGT-4. Moreover, miR-494 was down-regulated in esophageal cancer tissues and cells. xIST could sponge miR-494 and inhibition of miR-494 reversed the effects of xIST suppression on the malignant behaviors of TE-1 cells. Also, CDK6 was a target of miR-494 and CDK6 knockdown reversed the effects of miR-494 inhibition on the malignant behaviors of TE-1 cells. Besides, the expression of p-JAK2 and p-STAT3 was increased after miR-494 inhibition, which was reversed after inhibition of miR-494 and CDK6 at the same time. Conclusions: The data presented in this study revealed that xIST abnormal expression may play an oncogenic role in the development of esophageal cancer via miR-494/CDK6 axis through JAK2/STAT3 signal pathway. This study may provide theoretical basis for the molecular mechanism investigation of esophageal cancer.
暂无评论