LINC00657/miR-26a-5p/CKS2 ceRNA network promotes the growth of esophageal cancer cells via the MDM2/p53/Bcl2/Bax pathway

Abstract LncRNA LINC00657 has oncogenic or anti-carcinoma roles in different cancers, and yet its detailed molecular mechanism in esophageal cancer (EC) remains unclear. In addition, competitive endogenous RNA (ceRNA) regulatory lncRNA–miRNA–mRNA networks are critical for tumorigenesis and progression. Hence, the present study explored the roles of LINC00657 in EC and identified its relevant ceRNA network. We first detected the expression of LINC00657 in EC. Then, we applied starBase and TargetScan websites to find miR-26a-5p binding to LINC00657 and obtain CKS2 as a target of miR-26a-5p. The roles of LINC00657, miR-26a-5p or CKS2 in the proliferation, migration, invasion, and apoptosis of EC cells were respectively assessed by CCK-8, wound healing assay, transwell invasion assay, and flow cytometry. The changes of the MDM2/p53/Bcl2/Bax pathway were measured via Western blot. The results revealed that LINC00657 showed an aberrant high expression in EC cells, which promoted the growth of EC cells. Additionally, LINC00657 functioned as a sponge of miR-26a-5p, and LINC00657 negatively mediated miR-26a-5p to regulate the growth of EC cells. Furthermore, CKS2 was observed as a direct target of miR-26a-5p, and CKS2 controlled the growth of EC cells via the MDM2/p53/Bcl2/Bax pathway. Moreover, there was a positive correlation between LINC00657 and CKS2. LINC00657 knockdown inhibited CKS2 expression to suppress the proliferation, migration, and invasion of EC cells and induced apoptosis via regulating the MDM2/p53/Bcl2/Bax pathway. Collectively, LINC00657/miR-26a-5p/CKS2 ceRNA network could promote the progression of EC, which is good for understanding the molecular mechanism of EC and offers novel biomarkers for EC diagnosis and therapy.

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MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway

Bioscience Reports ◽

10.1042/bsr20201901 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Liang Zhang ◽

Zhuang Tong ◽

Zhe Sun ◽

Guolian Zhu ◽

Erdong Shen ◽

...

Keyword(s):

Esophageal Cancer ◽

Target Gene ◽

Opposite Effect ◽

Caspase 3 ◽

Malignant Tumors ◽

Luciferase Reporter ◽

Akt Pathway ◽

Migration And Invasion ◽

Ec Cells ◽

Esophageal Cancer Cells

Abstract Background: Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system. MiR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers. MiR-25-3p was found to be high expressed in the blood of EC patients. The aim of the present study was to explore the effect of miR-25-3p and its target gene on EC. Methods: miR-25-3p expression in the blood of EC patients and EC cells was detected by RT-qPCR. The target of miR-25-3p was identified by bioinformatics and luciferase reporter assay. After transfection, cell viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, wound healing, and transwell assays, respectively. The expressions of PTEN, Bax, Bcl-2, cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blot. Results: MiR-25-3p was high expressed in the blood of EC patients and EC cells. MiR-25-3p targeted PTEN and inhibited the expression of PTEN. MiR-25-3p mimic increased the viability, migration, invasion and the expressions of Bcl-2, and inhibited the apoptosis and the expression of Bax and cleaved caspase-3 in EC cells. MiR-25-3p mimic also enhanced the expressions of p-PI3K and p-AKT and the ratios of p-PI3K/PI3K and p-AKT/AKT in EC cells. PTEN overexpression not only had an opposite effect of miR-25-3p mimic, but also reversed the effect of miR-25-3p mimic on EC cells. Conclusion: MiR-25-3p targeted PTEN to promote the migration and invasion, and inhibit apoptosis of EC cells via the PI3K/AKT pathway, which might provide a new therapeutic target for EC treatment.

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LncRNA RP11-465B22.8 triggers esophageal cancer progression by targeting miR-765/KLK4 axis

Cell Death Discovery ◽

10.1038/s41420-021-00631-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Rui Hu ◽

Rui Bi ◽

Lianyong Jiang ◽

Haibo Xiao ◽

Xiao Xie ◽

...

Keyword(s):

Esophageal Cancer ◽

Cell Migration ◽

Cancer Progression ◽

Ectopic Expression ◽

Migration And Invasion ◽

M2 Macrophage ◽

Rna Seq ◽

Poor Survival ◽

Tumorigenesis And Progression ◽

Ec Cells

AbstractLncRNAs play an important role in tumorigenesis and progression; however, the function and mechanisms of lncRNAs in esophageal cancer (EC) remain largely unclear. In this study, we screened the differentially expressed lncRNAs in EC by using RNA-seq and one of the most upregulated lncRNAs, lncRNA RP11-465B22.8, was further characterized. LncRNA RP11-465B22.8 was upregulated in EC tissues and high lncRNA RP11-465B22.8 expression was associated with poor survival of EC patients. Ectopic expression of lncRNA RP11-465B22.8 enhanced the proliferation, migration, and invasion of EC cells, whereas knockdown of lncRNA RP11-465B22.8 led to the opposite effects. Mechanistically, lncRNA RP11-465B22.8 sponged miR-765 to increase the expression of KLK4. Moreover, LncRNA RP11-465B22.8 could be delivered from EC cells to macrophages via exosomes and subsequently induced M2 macrophage-induced cell migration and invasion. Our findings revealed a novel lncRNA RP11-465B22.8/miR-765/KLK4 pathway in EC and indicated that lncRNA RP11-465B22.8 might be a potential target for EC therapy.

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Aberrant hypermethylation-mediated downregulation of antisense lncRNA ZNF667-AS1 and its sense gene ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma

Cell Death and Disease ◽

10.1038/s41419-019-2171-3 ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 12

Author(s):

Zhiming Dong ◽

Shengmian Li ◽

Xuan Wu ◽

Yunfeng Niu ◽

Xiaoliang Liang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Proximal Promoter ◽

Migration And Invasion ◽

Esophageal Cancer Cells ◽

E Cadherin

AbstractNatural antisense lncRNAs can interfere with their corresponding sense transcript to elicit concordant or discordant regulation. LncRNA ZNF667-AS1 and its sense gene ZNF667 were found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues by RNA sequencing; however, the exact roles of both genes in ESCC occurrence and development have not been clarified. This study was to investigate the expression patterns, epigenetic inactivation mechanisms, function, and prognostic significance of ZNF667-AS1 and ZNF667 in ESCC tumorigenesis. Frequent downregulation of ZNF667-AS1 and ZNF667 was detected in esophageal cancer cells and ESCC tissues. The expression levels of ZNF667-AS1 and ZNF667 were significantly reversed by treatment with 5-Aza-dC and TSA in esophageal cancer cell lines. The CpG sites hypermethylation within proximal promoter influenced the binding ability of transcription factor E2F1 to the binding sites and then affected the transcription and expression of ZNF667-AS1 and ZNF667. Overexpression of ZNF667-AS1 and ZNF667 suppressed the viability, migration, and invasion of esophageal cancer cells in vitro. Overexpression of ZNF667-AS1 increased mRNA and protein expression level of ZNF667. ZNF667-AS1 interacts with and recruits TET1 to its target gene ZNF667 and E-cadherin to hydrolyze 5′-mc to 5′-hmc and further activates their expression, meanwhile, ZNF667-AS1 also interacts with UTX to decrease histone H3K27 tri-methylation to activate ZNF667 and E-cadherin expression. Furthermore, ZNF667-AS1 or ZNF667 expression and promoter methylation status were correlated with ESCC patients’ survival. Thus, these findings suggest that ZNF667-AS1 and ZNF667 may act as tumor suppressors and may serve as potential targets for antitumor therapy.

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Loss of G3BP1 suppresses proliferation, migration, and invasion of esophageal cancer cells via Wnt/β‐catenin and PI3K/AKT signaling pathways

Journal of Cellular Physiology ◽

10.1002/jcp.28648 ◽

2019 ◽

Vol 234 (11) ◽

pp. 20469-20484 ◽

Cited By ~ 12

Author(s):

Li‐Na Zhang ◽

Lei Zhao ◽

Xin‐Long Yan ◽

Ying‐Hui Huang

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Akt Signaling ◽

Migration And Invasion ◽

Esophageal Cancer Cells

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Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro

Cancer Cell International ◽

10.1186/s12935-019-1061-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Chengjuan Zhang ◽

Junxia Zhang ◽

Qiong Wu ◽

Benling Xu ◽

Guoguo Jin ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Cell Apoptosis ◽

Biological Effects ◽

Migration And Invasion ◽

Global Changes ◽

Fcm Analysis ◽

Esophageal Cancer Cells

Abstract Background As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer. Methods We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model. Results We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer. Conclusions Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2–CREB–Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer.

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IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2010.12.115 ◽

2011 ◽

Vol 404 (4) ◽

pp. 1070-1075 ◽

Cited By ~ 19

Author(s):

Kei Yoshino ◽

Satoru Motoyama ◽

Souichi Koyota ◽

Kaori Shibuya ◽

Shuetsu Usami ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Radiation Induced ◽

Induced Apoptosis ◽

Esophageal Cancer Cells

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Knockdown of lncRNA TUC338 inhibits esophageal cancer cells migration and invasion

Journal of Thoracic Disease ◽

10.21037/jtd-21-563 ◽

2021 ◽

Vol 13 (5) ◽

pp. 3061-3069

Author(s):

Ting Qian ◽

Hui Zhang ◽

Shaorong Yu ◽

Zhenzhang Chen ◽

Hui Jia ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Migration And Invasion ◽

Esophageal Cancer Cells

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α-bisabolol enhances radiotherapy-induced apoptosis in endometrial cancer cells by reducing the effect of XIAP on inhibiting caspase-3

Bioscience Reports ◽

10.1042/bsr20190696 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 1

Author(s):

Dongmei Fang ◽

Hongxin Wang ◽

Min Li ◽

Wenwen Wei

Keyword(s):

Endometrial Cancer ◽

Caspase 3 ◽

Migration And Invasion ◽

Inhibitor Of Apoptosis ◽

Downstream Effectors ◽

Apoptosis Protein ◽

Ec Cells ◽

Cox 2 ◽

Matrix Metalloproteinases 9 ◽

Induced Apoptosis

Abstract Endometrial cancer (EC) is one of the most common cancers in females. Although the diagnosis and treatment in early stages can greatly improve the survival rate of patients, the advanced EC still is lethal. Radiotherapy is widely used against EC, and it is a great challenge to find an effective way to overcome the resistance of EC during radiotherapy. α-bisabolol is a promising drug, which has already exhibited its anti-tumor effect in some malignancies. Here we reported that α-bisabolol could inhibit the proliferation of EC cells. It is also shown that their abilities of migration and invasion were effectively reduced by α-bisabolol. Furthermore, our results also demonstrated that α-bisabolol could improve sensitivity of EC cells in radiotherapy and further inhibited the growth of EC cells. By Western blot, we found the expression of matrix metalloproteinases-9 (MMP-9) and cyclin E were significantly decreased, which indicated that EC cells can be further suppressed by using α-bisabolol and radiotherapy. It is also demonstrated in our study that the rate of apoptotic cells is markedly increased in EC by using these two treatments. The significant decrease in X-linked inhibitor of apoptosis protein (XIAP) and increase in caspase-3 detected in our study suggested that the enhancement of apoptosis is mediated by XIAP/caspase-3 pathway, which was further confirmed by examining the downstream effectors of caspase-3, COX-2, PARP and cleaved PARP. In the present study, we demonstrated that α-bisabolol could enhance the sensitivity of EC cells to radiotherapy, which provide a novel alternative for overcoming radioresistance of EC cells and achieving a better outcome in radiotherapy.

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