Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model

Abstract BackgroundLong non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes the glioma progression.MethodsRNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays and a mouse xenograft model were performed to determine the functions of TMEM44-AS1. Co-IP, ChIP, Dual-luciferase reporter assays, RNA pulldown and RNA immunoprecipitation assays were performed to study the molecular mechanism of TMEM44-AS1 and the downstream target.ResultsWe identified a novel lncRNA TMEM44-AS1, which was aberrantly expressed in glioma tissues, and that increased TMEM44-AS1 expression was correlated with malignant progression and poor survival for patients with glioma. Expression of TMEM44-AS1 increased the proliferation, colony formation, migration, and invasion of glioma cells. Knockdown of TMEM44-AS1 in glioma cells reduced cell proliferation, colony formation, migration and invasion, and tumor growth in a nude mouse xenograft model. Mechanistically, TMEM44-AS1 is directly bound to the SerpinB3, and sequentially activated Myc signaling; Myc transcriptionally induced TMEM44-AS1 and directly bound to the promoter and super-enhancer of TMEM44-AS1, thus forming a positive feedback loop with TMEM44-AS. Further studies demonstrated that Myc interacts with MED1 regulates the super-enhancer of TMEM44-AS1. More importantly, a novel small-molecule Myc inhibitor, Myci975, alleviated TMEM44-AS1-promoted the growth of glioma cells. Finally, TMEM44-AS1 activated IL-6 signaling by recruiting EGR1 to the promoter of IL-6 in glioma cells. ConclusionsOur study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.

Download Full-text

Oxygen Is a Master Regulator of the Immunogenicity of Primary Human Glioma Cells

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2012.05.013 ◽

2012 ◽

Vol 2012 ◽

pp. 104

Author(s):

J. Uhm

Keyword(s):

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cells ◽

Master Regulator

Download Full-text

265: A Constitutively Activated Mutant form of Propsa that Manifests Catalytic Action Increases Cell Invasion in Vitro and Frequency of Pulmonary Metastases in vivo in a Subcutaneous Mouse Xenograft Model

The Journal of Urology ◽

10.1016/s0022-5347(18)30530-5 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 89-89

Author(s):

Sven Wenske ◽

Todd Hricik ◽

Brett S. Carver ◽

Matthew F. O'Brien ◽

Ruslan Korets ◽

...

Keyword(s):

Cell Invasion ◽

Pulmonary Metastases ◽

Xenograft Model ◽

Catalytic Action ◽

Mutant Form ◽

Mouse Xenograft ◽

Mouse Xenograft Model

Download Full-text

Mutant IκBα Suppresses Hypoxia-Induced VEGF Expression Through Downregulation of HIF-1α and COX-2 in Human Glioma Cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504005776367898 ◽

2005 ◽

Vol 15 (3) ◽

pp. 139-149 ◽

Cited By ~ 8

Author(s):

Yoshihira Kimba ◽

Tatsuya Abe ◽

Jian Liang Wu ◽

Ryo Inoue ◽

Minoru Fukiki ◽

...

Keyword(s):

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cells ◽

Vegf Expression ◽

Cox 2

Download Full-text

Differential expression and role of p21cip/waf1 and p27kip1 in TNF-α-induced inhibition of proliferation in human glioma cells

Molecular Cancer ◽

10.1186/1476-4598-6-42 ◽

2007 ◽

Vol 6 (1) ◽

pp. 42 ◽

Cited By ~ 17

Author(s):

Pabbisetty Kumar ◽

Anjali Shiras ◽

Gowry Das ◽

Jayashree C Jagtap ◽

Vandna Prasad ◽

...

Keyword(s):

Differential Expression ◽

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cells ◽

Inhibition Of Proliferation ◽

Tnf Α

Download Full-text

Arsenic nano complex induced degradation of YAP sensitized ESCC cancer cells to radiation and chemotherapy

Cell & Bioscience ◽

10.1186/s13578-020-00508-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Wei Zhou ◽

Meiyue Liu ◽

Xia Li ◽

Peng Zhang ◽

Jiong Li ◽

...

Keyword(s):

Transcription Factor ◽

Radiation Therapy ◽

Cancer Cells ◽

Solid Tumors ◽

Xenograft Model ◽

Ros Production ◽

Protective Effects ◽

Migration Ability ◽

Mouse Xenograft ◽

Mouse Xenograft Model

Abstract Background Increased reactive oxygen species (ROS) production by arsenic treatment in solid tumors showed to be effective to sensitize cancer cells to chemotherapies. Arsenic nano compounds are known to increase the ROS production in solid tumors. Methods In this study we developed arsenic–ferrosoferric oxide conjugated Nano Complex (As2S2–Fe3O4, AFCNC) to further promote the ROS induction ability of arsenic reagent in solid tumors. We screen for the molecular pathways that are affect by arsenic treatment in ESCC cancer cells. And explored the underlying molecular mechanism for the arsenic mediated degradations of the key transcription factor we identified in the gene microarray screen. Mouse xenograft model were used to further verify the synthetic effects of AFCNC with chemo and radiation therapies, and the molecular target of arsenic treatment is verified with IHC analysis. Results With gene expression microarray analysis we found Hippo signaling pathway is specifically affected by arsenic treatment, and induced ubiquitination mediated degradation of YAP in KYSE-450 esophageal squamous cell carcinoma (ESCC) cells. Mechanistically we proved PML physically interacted with YAP, and arsenic induced degradation PML mediated the degradation of YAP in ESCC cells. As a cancer stem cell related transcription factor, YAP 5SA over expressions in cancer cells are correlated with resistance to chemo and radiation therapies. We found AFCNC treatment inhibited the increased invasion and migration ability of YAP 5SA overexpressing KYSE-450 cells. AFCNC treatment also effectively reversed protective effects of YAP 5SA overexpression against cisplatin induced apoptosis in KYSE-450 cells. Lastly, with ESCC mouse xenograft model we found AFCNC combined with cisplatin treatment or radiation therapy significantly reduced the tumor volumes in vivo in the xenograft ESCC tumors. Conclusions Together, these findings suggested besides ROS, YAP is a potential target for arsenic based therapy in ESCC, which should play an important role in the synthetic effects of arsenic nano complex with chemo and radiation therapy.

Download Full-text

Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01882-1 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Zizhen Si ◽

Lei Yu ◽

Haoyu Jing ◽

Lun Wu ◽

Xidi Wang

Keyword(s):

Colorectal Cancer ◽

Rna Binding ◽

Xenograft Model ◽

Luciferase Reporter ◽

Cancer Proliferation ◽

Mouse Xenograft ◽

Mouse Xenograft Model

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

Download Full-text