Long noncoding RNA CASC9/miR‐519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

Liu, Hongjiang; Li, Chen; Yang, Jian; Sun, Yuchen; Zhang, Shunyao; Yang, Jianhui; Yang, Liang; Wang, Yuanyu; Jiao, Baohua

doi:10.1111/jcmm.13932

Cited by 52 publications

(36 citation statements)

References 30 publications

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“…Ectopic expression of CASC9 also occurs in gastric cancer, where CASC9 knockdown facilitates GC cell apoptosis [16]. In addition, the expression of CASC9 has been conformed higher in glioma tissues and cells, and CASC9 silencing hampered cell proliferative ability as well as invasion [30]. These findings demonstrated that regulating the expression of CASC9 may affect BC progression.…”

Section: Discussionmentioning

confidence: 99%

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CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

Huo

Tan

Chen

2020

Nephron

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Background: As the seventh most common urologic carcinoma worldwide, approximately 430,000 patients are diagnosed with bladder cancer (BC) every year. Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the progression of BC. Objectives: This study is aimed to explore the function and mechanism of CASC9 in BC. Methods: Bioinformatics analysis and experiments including RT-qPCR, luciferase reporter, Cell Counting Kit-8 assay, Western blot, RNA immunoprecipitation assay, and TU-NEL staining were applied to explore the function and mechanism of CASC9 in BC tissues and cell lines. Results: Our study demonstrated that CASC9 was upregulated in BC tissues and cell lines. Moreover, we found that CASC9 knockdown notably decreased proliferation while increased apoptotic rate in BC cells. Mechanistically, bioinformatics prediction and following experiments indicated that CASC9 worked as a competing endogenous RNA (ceRNA) of CBX2 through sponging miR-497-5p. Meanwhile, we recognized that CASC9 and miR-497-5p negatively regulated each other in a mutual way. Furthermore, we found that miR-497-5p shared binding site with CBX2. In addition, miR-497-5p could negatively regulated CBX2, while CASC9 could positively regulated CBX2. Rescue assays reveled that CBX2 overexpression could reversed the reduction of cell proliferation or the enhancement of cell apoptosis induced by CASC9 suppression. Conclusions: Our study manifests the first evidence that CASC9 serves as an oncogene in BC and accelerates cell proliferation by modulating miR-497-5p/CBX2 axis. The present study may provide a cogitable target for BC therapy.

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Section: Discussionmentioning

confidence: 99%

“…It is well known that lncRNAs could serve as spongers for miRNAs [35]. Moreover, CASC9 has been certified to be capable of accelerating cancer development via sponging miRNAs, including ovarian cancer, glioma, and breast cancer [15, 30, 36]. Therefore, we explored whether CASC9 affected BC progression in a similar way.…”

Section: Discussionmentioning

confidence: 99%

CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

Huo

Tan

Chen

2020

Nephron

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“…Although we found the high expression of DLEU1 in GBM, the regulatory mechanism involved in DLEU1 up-regulation remained elusive. Existing evidences report that several key transcription factors contribute to the up-regulation of lncRNA in human cancers, such as SP1, ELK1, STAT3 and YY1 [30][31][32][33][34]. Using UCSC tool, SP1 was predicted as a transcription factor of DLEU1.…”

Section: The Transcription Factor Sp1 Contributed To the Up-regulatiomentioning

confidence: 99%

SP1–DLEU1–miR-4429 feedback loop promotes cell proliferative and anti-apoptotic abilities in human glioblastoma

Chen

Liu

2019

Bioscience Reports

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Mounting studies have revealed that long non-coding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) positively regulated the initiation and development of various human malignant tumors. Nevertheless, the function and mechanism of DLEU1 in human glioblastoma multiforme (GBM) remain elusive and ill-defined. The current study was designed to highlight the functional role and disclose the underlying molecular mechanism by which DLEU1 regulated GBM development. We found that DLEU1 was up-regulated in GBM and DLEU1 knockdown significantly inhibited GBM cell proliferation and induced apoptosis. As predicted by bioinformatics analysis and validated in mechanistic assays, SP1 could bind to the promoter region of DLEU1 to activate DLEU1 transcription. Additionally, miR-4429 was verified as a target gene of DLEU1 and negatively modulated by DLEU1. More importantly, miR-4429 overexpression repressed the mRNA and protein levels of SP1 via binding to the 3′UTR of SP1. Overexpression of SP1 or miR-4429 inhibitor could partly abolish the effect of DLEU1 knockdown on cell viability and apoptosis in GBM. Accordingly, our experimental data revealed that SP1–DLEU1–miR-4429 formed a feedback loop to promote GBM development, providing a new evidence for the role of DLEU1 in GBM.

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“…The prognostic factors for glioma consist of age, Karnofsky performance status (KPS) score, histologic grade, tumor necrosis, preoperative duration of symptoms, surgical resection extent and multimodal therapeutic strategies [3]. Glioma is characterized by diffusion and high invasiveness, but its potential mechanisms is still far from understanding [4]. Therefore, it is an urgent need to find new and effective strategies and establish potential therapeutic targets for the treatment of human glioma.…”

Section: Introductionmentioning

confidence: 99%

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Yang

Wang

et al. 2020

Cancer Cell Int

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Background: Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3). Methods: Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was cocultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8 + T cells were isolated. CD8 + T cells were co-cultured with U87 cells to detect the CD8 + T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8 + T cells was detected. Results: PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8 + T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8 + T cells in glioma mice.

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Long noncoding RNA CASC9/miR‐519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

Cited by 52 publications

References 30 publications

CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

SP1–DLEU1–miR-4429 feedback loop promotes cell proliferative and anti-apoptotic abilities in human glioblastoma

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

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