BACKGROUND: Aberrant expression of long non-coding RNAs (lncRNAs) can contribute to the pathogenesis of coronary artery disease (CAD). In this study, we aimed to evaluate the expression of lncRNA interferon γ-antisense 1 (IFNG-AS1), zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), and their direct target genes (IFN-γ and ZEB2, respectively) in peripheral blood mononuclear cell (PBMC) from CAD and healthy individuals.
RESULTS: We recruited 40 CAD patients and 40 healthy individuals. After doing some bioinformatics analyses, the expressions of IFNG-AS1/ ZEB2-AS1 lncRNAs and IFN-γ/ ZEB2 in PBMCs were measured using quantitative real-time PCR. The possible correlation between the putative lncRNAs and disease severity was also assessed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive role of lncRNAs as diagnostic biomarkers in CAD patients. The expressions of IFNG-AS1 lncRNA as well as IFN-γ and ZEB2 genes were significantly reduced in CAD patients compared to healthy subjects. In contrast, the expression of ZEB2-AS1 was up-regulated in these patients. Linear regression analysis unveiled that there is a positive correlation between the expression of IFNG-AS1 and IFN-γ, also similarly, ZEB2-AS1 and ZEB2 in PBMCs of subjects. Moreover, the expression of IFNG-AS1 and ZEB2-AS1 correlated with the Gensini score. The area under the ROC curves ranged from 0.633-0.742 for ZEB2-AS1/ZEB2 and IFNG-AS1/IFN-γ, respectively.
CONCLUSIONS: Our results indicated that the dysregulation of IFNG-AS1/IFN-γ and ZEB2-AS1/ZEB2 in PBMCs of CAD patients may be involved in CAD pathogenesis.

Long non-coding RNAs (LncRNAs) are eminent genes in the human genome that interfere with the regulation of many complexities of organisms and control many of the various biological processes. As a result, it is considered that they may play an important role in different cancers. With regard to the high prevalence of breast cancer and the role of lncRNA, the present study aimed at investigating the expression of various lncRNAs.
Fresh tissues were obtained from operating rooms of Shariati, Khatamolanbia, and Milad Hospitals (Tehran, Iran) by a surgeon. A total of 45 tumor samples and 45 non-tumor samples (from the margin of tumor) were obtained from the same patients. Relative expression evaluation method was used in Real time PCR. Estrogenn receptor (ER), progesterone receptor (PR), and HER2 expression were analyzed using IHC analyses of each cell block.
Participants included 44 female and 1 male with the mean age ± SD of 50 ± 12.0 years (range: 23-74). A majority of participants (41/45) were Ductal carcinoma type. Our results showed significant expressions for CBR3-AS1 (P-value=0.0139), RAB6C-AS1 (P-value=0.0023), and ZEB2-AS1 (P-value=0.0289) in comparison with the healthy cells. ROC curve analysis for CBR3-AS1 LncRNA revaled sensitivity more than 70%.
Although CBR3-AS1, RAB6C-AS1, and ZEB2-AS1 lncRNAs were found to have high expressions in the breast cancer cells, only CBR3-AS1 lncRNA has a high chance to be a breast cancer biomarker.
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Background: Long non-coding RNA Zinc finger E-box binding homeobox 2 (ZEB2) antisense RNA 1 (ZEB2-AS1) has been shown to promote tumor progression. However, the clinical significance and fundamental function role of ZEB2-AS1 in osteosarcoma (OS) has been poorly understood. Methods: The expression of ZEB2-AS1 was determined in tumor tissues and matched normal tissues from 67 OS patients using quantitative reverse transcriptase PCR analysis. Clinical value of ZEB2-AS1 was evaluated by χ2 test and Kaplan-Meier method. Cell proliferation was analyzed using CCK-8 assay, colony formation. Cell apoptosis status was determined by caspase-3 activity assay. Cell migration, invasion and epithelial-mesenchymal transition (EMT) were investigated by scratch wound healing, transwell invasion assays and Western blotting. Results: Clinical association analysis revealed that high ZEB2-AS1 expression correlated with tumor size, distant metastasis and poor prognosis of OS patients. Moreover, ZEB2-AS1 expression was identified as an independent prognostic factor for OS patients. Loss-of-function assays demonstrated that ZEB2-AS1 knockdown suppressed the proliferation and induced apoptosis in OS cells. In addition, ZEB2-AS1 knockdown inhibited cell migration, invasion, EMT of OS cells in vitro. Conclusions: Taken together, our data demonstrate that ZEB2-AS1 serves a putative oncogenic role and associates with unfavorable prognosis in OS.

Non-small cell lung cancer (NSCLC) remains the most common cause of human cancer-related death worldwide, and the present study aims to explore the roles of long non-coding (lnc)RNA ZEB2-AS1 in NSCLC and the related mechanism.
Quantitative real-time-polymerase chain reaction was performed to compare the expressions of ZEB2-AS1 in NSCLC cancer tissue and the adjacent non-tumorous tissues. The diagnostic and prognostic roles of ZEB2-AS1 in NSCLC were also evaluated by the receiver operating characteristic curve and the Kaplan-Meier survival analysis. NSCLC cell line A549 cells were transfected with ZEB2-AS1 siRNA, and the cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) of the ZEB2-AS1 siRNA group and control group were compared.
ZEB2-AS1 was significantly increased in NSCLC tissues. The knockdown of ZEB2-AS1 markedly inhibited the cell viability, migration, invasion, and EMT of A549 cells in vitro.
ZEB2-AS1 was up-regulated in NSCLC, and it may serve as a potential target for the diagnosis, prognosis, and treatment of NSCLC.

Background: Accumulating reports have demonstrated that long-noncoding RNAs (lncRNAs) play critical roles in the pathological progression of colorectal cancer (CRC). However, the role of lncRNA zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in CRC remains largely unknown. Methods: The authors detected the ZEB2-AS1 expression in CRC tissue sample and CRC cell lines. The effects of ZEB2-AS1 on CRC were identified through in vitro assays (i.e., transwell assay, wound-healing assay, immunofluorescence assay, and Western blot) in a ZEB2-AS1 knockdown system. The molecular mechanism of ZEB2-AS1 was explored via bioinformatic tools, quantitative real-time polymerase chain reaction (qRT-PCR), dual-luciferase reporter assay, RNA immunoprecipitation assay, and so on. Moreover, a series of gain-of-function experiments were performed to identify the effect of ZEB2-AS1 and miR-1205 on epithelial-to-mesenchymal transition (EMT) in CRC cells. Results: This analysis clarified that ZEB2-AS1 was upregulated in both CRC tissue sample and cells lines; meanwhile, the high expression of ZEB2-AS1 was correlated with poor overall survival rate. ZEB2-AS1 knockdown significantly suppresses the EMT in CRC cells. Furthermore, the authors identified that the expression of ZEB2-AS1 was negatively correlated with expression of miR-1205, and CRKL could be a direct target of miR-1205. Through the gain-of-function experiments, they found that ZEB2-AS1 accelerates EMT in CRC cells via modulating the expression of miR-1205 and CRKL. Conclusion: Taken together, this study revealed that ZEB2-AS1 accelerates EMT in CRC through the miR-1205/CRKL pathway, suggesting that ZEB2-AS1 may potentially serve as a target of CRC.

UNASSIGNED: To investigate the role of zinc finger E‑box‑binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in regulating laryngeal squamous cell carcinoma (LSCC) progression.
UNASSIGNED: In this retrospective study, we included all patients who underwent a surgical operation at The First Hospital of Qiqihaer City for LSCC. Then, we compared the expression of ZEB2-AS1 in LSCC tissues and paired healthy tissues. Besides, we also performed a series of functional assays, CCK8 assays, colony formation assays, and transwell assays to examine the functions of LSCC cells after knockdown of ZEB2-AS1. Through bioinformatics analysis, we predicted that ZEB2-AS1 binds to miR-6840-3p and targets PLXNB1.
UNASSIGNED: We indicated that the expression of ZEB2-AS1 was higher in LSCC tissues compared to the paired adjacent tissues, and ZEB2-AS1 was also highly expressed in LSCC cell lines. Furthermore, we discovered that ZEB2-AS1 promoted cell proliferation, migration and invasion and was associated with poor prognosis. To find the mechanism, we performed bioinformatics analysis. We identified that ZEB2-AS1 binds to miR-6840-3p and targets PLXNB1. Additionally, miR-6840-3p overexpression or knockdown of PLXNB1 decreased the abilities of cell migration and invasion.
UNASSIGNED: These findings demonstrated that overexpression of ZEB2-AS1 promotes LSCC progression. Overexpression of miR-6840-3p or downregulation of PLXNB1 can abrogate ZEB2-AS1-mediated LSCC malignant development.

Colon cancer (CC) is the third most common cancer and the fourth leading cause of cancer-associated death in the world. Long non-coding RNA (lncRNA) ZEB2-AS1 was reported to be dysregulated and play important roles in multiple human cancers. However, the expression level and functions of ZEB2-AS1 in colon cancer is unknown. Here, we firstly observed that ZEB2-AS1 was significantly upregulated in colon cancer and predicted a poor prognosis. Functional assays showed that silencing ZEB2-AS1 expression remarkably inhibited proliferation, suppressed cell cycle transition while induced apoptosis in CC cells. In addition, miR-143 was demonstrated to act as a tumor suppressor and predicted as a downstream target of ZEB2-AS1 in CC. Furthermore, bcl-2 was identified as a direct target of miR-143 and ZEB2-AS1 could regulate the expression of bcl-2 via miR-143 in CC. A rescue assay indicated that downregulation of miR-143 partly abolished the suppressive effect of ZEB2-AS1 silencing on CC cells proliferation. Collectively, our results revealed that ZEB2-AS1 was upregualted and functioned as an oncogene via regulating miR-143/bcl-2 axis in colon cancer. These findings suggest that ZEB2-AS1 may serve a novel biomarker in the diagnosis and a potential therapeutic target in the treatment of colon cancer.

Pre-eclampsia (PE) is a pregnancy disease that causes maternal death and threatens the health of newborns. Accumulating evidence has revealed the essential roles of long noncoding RNAs (lncRNAs) in the progression of PE. The present investigation determined lncRNA ZEB2 antisense RNA 1 (ZEB2-AS1) expression in PE and looked into the potential role of ZEB2-AS1 in modulating trophoblastic cell functions. Quantitative real-time polymerase chain reaction evaluated gene expression. Western blot analyzed the placental growth factor (PGF) protein level. Cell counting kit-8 and Transwell invasion assays assessed the proliferative and invasive abilities of placental trophoblast cells, respectively. Wound healing assay determined cell migratory potentials. Dual-luciferase reporter assay assessed the targeting relationship among ZEB2-AS1, miR-149, and PGF. Downregulation of lncRNA ZEB2-AS1 was detected in placentas from patients with PE when compared with those from normal pregnancies. Moreover, ZEB2-AS1 upregulation markedly promoted proliferative, migratory, and invasive potentials in HTR-8/SVneo cells, while knockdown of ZEB2-AS1 had the opposite effects. The effects on HTR-8/SVneo cells mediated by ZEB2-AS1 was correlated with the miR-149/PGF axis. These findings indicate that ZEB2-AS1 contributes to PE progression by affecting cell proliferative and invasive capacities via the miR-149/PGF axis in HTR-8/SVneo cells. In sum, we identified that ZEB2-AS1 was a novel aberrantly expressed lncRNA in the placentas of PE patients and lncRNA ZEB2-AS1 modulated trophoblastic cell line HTR-8/SVneo\'s proliferative and invasive potentials via targeting the miR-149/PGF axis.

The long noncoding RNAs (lncRNAs) have been increasingly appreciated as key players underlying tumourigenesis and hold great potentials as prognostic biomarkers and therapeutic targets. However, their roles in head neck squamous cell carcinoma (HNSCC) have remained incompletely known. Here, we sought to reveal the oncogenic roles and clinical significance of a tumour-associated lncRNA, zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), in HNSCC. ZEB2-AS1 was aberrantly overexpressed in a fraction of HNSCC samples. Its overexpression significantly associated with large tumour size, cervical node metastasis and reduced overall and disease-free survival. Antisense oligonucleotides (ASO)-mediated ZEB2-AS1 depletion markedly inhibited cell proliferation, migration and invasion while triggered apoptosis in HNSCC cells in part via modulating ZEB2 mRNA stability. Enforced overexpression of ZEB2 largely attenuated the phenotypic changes resulted from ZEB2-AS1 inhibition except the impaired cell proliferation. In addition, ZEB2-AS1 was required for TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro. Significantly reduced tumour growth and lung metastasis were observed in ZEB2-AS1-depleted cells in HNSCC xenograft animal models. Taken together, our findings reveal that overexpression of ZEB2-AS1 associates with tumour aggressiveness and unfavourable prognosis by serving as a putative oncogenic lncRNA and a novel prognostic biomarker in HNSCC.

BACKGROUND: Growing evidence has implicated the important role of the long non-coding RNAs (lncRNAs) in gastric cancer progression. In this study, we examined the expression of lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in gastric cancer tissues and elucidated the molecular mechanisms underlying ZEB2-AS1-mediated gastric cancer progression.
METHODS: Quantitative real-time PCR measured the gene expression level; CCK-8, colony formation and cell invasion assays determined gastric cancer cell proliferation, growth and invasion, respectively; the xenograft nude mice model was used to determine in vivo tumor growth; Bioinformatics analysis and luciferase reporter assay determined the downstream targets of ZEB2-AS1 and miR-143-5p. The expression of ZEB2-AS1 was upregulated in gastric cancer cell lines.
RESULTS: Knockdown of ZEB2-AS1 suppressed gastric cancer cell proliferation, growth and invasion, and also suppressed in vivo tumor growth in the nude mice. Overexpression of ZEB2-AS1 potentiated gastric cancer cell proliferation, growth and invasion. Bioinformatics analysis and luciferase reporter assay showed that miR-143-5p was a direct target of ZEB2-AS1 and was negatively regulated by ZEB2-AS1. Furthermore, hypoxia-inducible factor-1α (HIF-1α) was found to be a target of miR-143-5p and was negatively regulated by miR-143-5p. The rescue in vitro assays showed that the effects of ZEB2-AS1 overexpression on gastric cancer cell proliferation, growth and invasion was mediated via miR-143-5p/HIF-1α. ZEB2-AS1 and HIF-1α was upregulated in gastric cancer tissues, while miR-143-5p was down-regulated; and ZEB2-AS1 expression level was inversely correlated with miR-143-5p expression level, and positively correlated with HIF-1α mRNA expression level; while miR-143-5p expression level was inversely correlated with HIF-1α expression level. High ZEB2-AS1 expression level was correlated with poor differentiation, lymph node metastasis and distant metastasis.
CONCLUSIONS: Collectively, our results indicated that ZEB2-AS1 was up-regulated in gastric cancer tissues and cells and promoted cell proliferation and metastasis through miR-143-5p/HIF-1α pathway, which may provide a promising target for treatment of gastric cancer.