Publications by authors named "Huairui Chen"

9 Publications

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miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5.

Front Oncol 2021 23;11:600451. Epub 2021 Apr 23.

Department of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p-induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both and , and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.
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http://dx.doi.org/10.3389/fonc.2021.600451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103841PMC
April 2021

Facile Interfacial Synthesis of Densely Spiky Gold Nano-Chestnuts With Full Spectral Absorption for Photothermal Therapy.

Front Bioeng Biotechnol 2020 26;8:599040. Epub 2020 Oct 26.

Department of Neurosurgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

The gold nanostructure is regarded as the most promising photothermal agent due to its strong localized surface plasma resonance (LSPR) effect. In particular, the gold nanostructures with sharp spikes on the surface have higher optical signal enhancement, owing to the sharp tips drastically enhancing the intense nanoantenna effect. However, current approaches for the synthesis of spiky gold nanostructures are either costly, complicated, or uncontrollable. Herein, we report a novel strategy to synthesize gold nano-chestnuts (SGNCs) with sharp spikes as an excellent photothermal agent. The SGNCs were prepared by a facile one-pot interfacial synthetic method, and their controllable preparation mechanism was acquired. The SGNCs exhibited ideal full-spectrum absorption and showed excellent photothermal effect. They have a photothermal conversion efficiency (η) as high as 52.9%, which is much higher than traditional photothermal agents. The and results show that the SGNCs could efficiently ablate the tumor cells. Thus, the SGNCs have great potential in photothermal therapy applied in malignant tumors.
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http://dx.doi.org/10.3389/fbioe.2020.599040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649415PMC
October 2020

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1.

Oncol Rep 2020 Dec 15;44(6):2559-2568. Epub 2020 Oct 15.

Department of Neurosurgery, Changzheng Hospital, Navy Medical University, Shanghai 200003, P.R. China.

Alterations in the expression of microRNA (miR)‑138 have been demonstrated to result in the development of several malignant tumours. However, the possible function of miR‑138 in human glioma cells remains unclear. The present study demonstrated that miR‑138 was significantly downregulated in 48 human glioma specimens by quantitative PCR analysis. The upregulation of miR‑138 exerted significant antiproliferative and anti‑invasive effects on glioma cells and promoted their apoptosis. In addition, cAMP response element‑binding protein 1 (CREB1) was confirmed as a direct target gene of miR‑138 by luciferase gene reporter assay, and the antitumour effect of miR‑138 on glioma cells was significantly reversed by CREB1 overexpression. Moreover, the molecular mechanisms underlying the tumour‑suppressive role of miR‑138 in malignant glioma may be associated with the dephosphorylation of AKT/mTOR caused by the miR‑138 upregulation‑induced decrease in CREB1 expression in glioma cells. The results of the present study indicated that miR‑138 may affect CREB1/AKT/mTOR signalling to regulate the proliferation, apoptosis and invasion of glioma cells and the malignant progression of glioma, thereby suggesting that miR‑138 may be a potential target for the treatment of gliomas.
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http://dx.doi.org/10.3892/or.2020.7809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640360PMC
December 2020

Increased RLIP76 expression in IDH1 wild‑type glioblastoma multiforme is associated with worse prognosis.

Oncol Rep 2020 Jan 30;43(1):188-200. Epub 2019 Oct 30.

Department of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.

Mutation of the isocitrate dehydrogenase (IDH) gene is regarded a novel indicator for the prognosis of patients with glioma. However, the role of the IDH1 gene mutations in carcinogenesis and the mechanisms underlying their function in glioblastoma multiforme (GBM) remain unknown. The present study aimed to determine whether the association of RLIP76 with the different IDH1 mutational status could serve as a putative biomarker for improving disease prognosis. Quantitative PCR, western blotting and immunohistochemical staining assays were used to investigate the expression levels of RLIP76 in 124 patients with GBM with different IDH1 mutational status. In addition, the association between RLIP76 expression, IDH1 mutational status and clinicopathological characteristics was investigated. The effects of RLIP76 expression and IDH1 mutational status on cell proliferation, cell apoptosis, and cell signaling were examined by Cell Counting Kit‑8, flow cytometry and western blot assays, respectively. The data demonstrated that IDH1 wild‑type (IDH1Wt) patients with low RLIP76 expression exhibited improved overall and progression‑free survival. This effect was not observed in patients with IDH1 mutant (IDH1Mut) GBM. In vitro assays demonstrated that knockdown of IDH1 or overexpression of the IDH1 R132H mutation suppressed cell proliferation and promoted cell apoptosis in U87 glioma cells. Mechanistic studies further indicated that although the IDH1 R132H mutant phenotype exhibited similar antitumor effects on GBM cells as those observed with the IDH1 knockdown, it acted via a different mechanism with regard to the regulation of the apoptosis signaling pathway. IDH1 R132H mutant cells promoted p53‑induced apoptosis, while the IDH1 knockdown inhibited the RLIP76‑dependent apoptotic pathway in glioma cells. The findings of the present study provided insight to the contribution of IDH1 mutation in the development of GBM and indicated that RLIP76 may be considered as a prognostic biomarker of IDH1Wt GBM.
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http://dx.doi.org/10.3892/or.2019.7394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908935PMC
January 2020

A novel lncRNA-LINC01116 regulates tumorigenesis of glioma by targeting VEGFA.

Int J Cancer 2020 01 11;146(1):248-261. Epub 2019 Jun 11.

Department of Neurosurgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.
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http://dx.doi.org/10.1002/ijc.32483DOI Listing
January 2020

PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal transition signaling in glioblastoma.

Oncol Rep 2017 Nov 19;38(5):2911-2918. Epub 2017 Sep 19.

Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.

Temozolomide (TMZ) is commonly used in glioblastoma (GBM) chemotherapy. However, a great challenge for TMZ treatment is the rapid development of resistance and subsequent tumor recurrence and poor outcome. In the present study we established TMZ-resistant GBM cells (U87-TR and U251-TR) and found that the expression of PomGnT1 was significantly upregulated in TMZ-resistant GBM cells compared with the TMZ-sensitive counterparts. Furthermore, overexpression of PomGnT1 in U87-MG and U251-MG cells led to increased IC50 values for TMZ and reduced apoptosis of cells. Knockdown of PomGnT1 in both U87-TR and U251-TR cells led to decreased IC50 values for TMZ and enhanced apoptosis. Biochemical analysis revealed that PomGnT1 regulates the expression of factors in epithelial-mesenchymal transition signaling including TCF8, vimentin, β-catenin and Slug in GBM cells. These findings demonstrate that PomGnT1 might be a new focus of GBM research for treatment of recurrent TMZ-resistant GBM.
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http://dx.doi.org/10.3892/or.2017.5964DOI Listing
November 2017

Expression and functional implications of USP17 in glioma.

Neurosci Lett 2016 Mar 14;616:125-31. Epub 2016 Jan 14.

Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China. Electronic address:

Glioma is the most common and malignant brain tumor with extremely poor prognosis. It is crucial to understand the molecular characteristics of glioma and find out more effective therapeutic targets for the treatment of glioma. USP17 is a novel deubiquitinating enzyme that is differentially expressed in certain types of solid tumor. Our present study investigated the pathological functions and clinical significance of USP17 in glioma for the first time. We found that USP17 was down-regulated in glioma tissue compared with normal tissues. Overexpression of USP17 in glioma cells reduced their tumorigenesis and proliferation ability through reducing Ras and Myc protein levels. Subsequent in vivo experiments showed that overexpression of USP17 suppressed tumor progression in an orthotopic glioma models. Further, study of a cohort of 104 patients with stage I-IV glioma showed that USP17 expression was negatively associated with the WHO grade (p<0.001). USP17 was more highly expressed in low grade (I+II) glioma than high-grade (III+IV) glioma (p<0.001). Taken together, our results indicate that USP17 might play important functions in glioma through suppressing glioma tumorigenesis and proliferation.
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http://dx.doi.org/10.1016/j.neulet.2016.01.015DOI Listing
March 2016

Analysis of the embolization spinal dural arteriovenous fistula and surgical treatments on 52 cases of the patients.

Int J Clin Exp Med 2014 15;7(9):3062-71. Epub 2014 Sep 15.

Department of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai, China.

Background: Spinal dural arteriovenous fistula (SDAVF) highly threatens people's life and health. Effective methods for the diagnosis and treatment of the disease are badly needed in clinical application.

Objective: The objective of the present study was to sum up the diagnosis and treatment method of SDAVF to improve the diagnosis and treatment effect of the disease.

Methods: The epidemiological data, imaging data, therapeutic methods and postoperative follow-up data of 52 cases of patients with SDAVF received in our hospital in recent 6 years were collected and retrospectively analyzed.

Results: There were 43 male patients and 9 female patients with ages of 39-77 years and average age of 59.6 years. The course of disease was 1 to 48 months with an average disease course of 14.4 months. All the patients had syndromes of lower limb numbness, pain, weakness and other sensory and movement disorders mostly accompanied with defecation dysfunction. Magnetic resonance imaging (MRI) results demonstrated that spinal cord abnormalities were found in spinal cord, which could be diagnosed by digital subtraction angiography (DSA) examination. There were 40 cases received surgical treatment and there was no recurrence in the follow-up. There were 12 patients received embolotherapy, of whom 3 patients were operated the second time and 2 patients had embolization again. After 0.5-6 years of follow-up, postoperative symptoms of the 40 patients were improved in different degrees. The modified Aminoff-Logue function scoring was significantly decreased after treatment.

Conclusion: SDAVF is the easily diagnosed and delayed spinal cord vascular lesions in clinical applications. The diagnosis relies mainly on MRI and DSA examinations. The surgical treatment effect is good and is not easily relapsed. The trauma of the interventional embolization treatment is small, but the recurrence rate is high.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211832PMC
October 2014

Hypoxia-induced miR-497 decreases glioma cell sensitivity to TMZ by inhibiting apoptosis.

FEBS Lett 2014 Sep 29;588(18):3333-9. Epub 2014 Jul 29.

The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.

Understanding the resistance of glioma cells to chemotherapy has been an enormous challenge. In particular, mechanisms by which tumor cells acquire resistance to chemotherapy under hypoxic conditions are not fully understood. In this study, we have found that miR-497 is overexpressed in glioma and that hypoxia can induce the expression of miR-497 at the transcriptional level by binding with the hypoxia response element in the promoter. Ectopic overexpression of miR-497 promotes chemotherapy resistance in glioma cells by targeting PDCD4, a tumor suppressor that is involved in apoptosis. In contrast, the inhibition of miR-497 enhances apoptosis and increases the sensitivity of glioma cells to TMZ. These results suggest that miR-497 is a potential molecular target for glioma therapy.
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http://dx.doi.org/10.1016/j.febslet.2014.07.021DOI Listing
September 2014