Publications by authors named "Linaer Gu"

5 Publications

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The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis.

Biochem Biophys Res Commun 2021 Oct 28;572:20-26. Epub 2021 Jul 28.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Tongji University Cancer Center, Shanghai, China. Electronic address:

PYCR2 has previously been shown to be related to a range of malignancies including hepatocellular carcinoma and melanoma, but its mechanistic functions and prognostic relevance in colon cancer patients remain to be defined. Herein, we used the Oncomine, Human Protein Atlas, The Cancer Genome Atlas (TCGA), and UALCAN databases to explore the expression of this gene in different human cancer, after which the relationship between PYCR2 expression and patient clinicopathologic characteristics was evaluated. We utilized an in vitro approach to evaluate the association between PYCR2 expression and colon cancer cell proliferation, migration, invasion, and tumor microsphere formation. The cell apoptosis was analyzed by flow cytometry. Gene set enrichment analysis (GSEA) approaches were additionally used to probe signaling pathways related to PYCR2. These analyses confirmed that PYCR2 was upregulated in several cancer types including colon cancer, with such upregulation correlating with a poor patient prognosis and with malignant clinicopathological characteristics. PYCR2 expression was identified as an independent predictor of colon cancer patients' survival, and in vitro analyses suggested that knocking down this gene was sufficient to disrupt the proliferative, migratory, invasive, and microsphere formation activities of colon cancer cells. Moreover, shPYCR2 transfection induced colon cancer cell apoptosis. GSEA suggested that high PYCR2 expression correlates with the differential enrichment of the Wnt β-catenin signaling, MYC targets, RNA polymerase, and Notch signaling pathways. Overall, these data indicate that PYCR2 is an important mediator of tumor progression and metastasis, and suggest that it may be a valuable prognostic indicator for colon cancer patient evaluation.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.084DOI Listing
October 2021

Targeting STAT3 enhances NDV-induced immunogenic cell death in prostate cancer cells.

J Cell Mol Med 2020 04 26;24(7):4286-4297. Epub 2020 Feb 26.

Department of Medical Oncology, Shanghai Tenths People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Oncolytic Newcastle disease virus (NDV) induces immunogenic cell death (ICD), liberating danger-associated molecular patterns (DAMPs) that provokes defiance in neoplastic malignancy. The present study aims to investigate whether and how oncolytic NDV triggers ICD in prostate cancer cells. We show that NDV/FMW, an oncolytic NDV strain FMW, elicited the expression and release of several ICD markers, that is calreticulin (CRT), heat shock proteins (HSP70/90) and high-mobility group box 1 (HMGB1), in prostate cancer cells. Furthermore, pharmacological repression of apoptosis, necroptosis, autophagy or endoplasmic reticulum (ER) stress exerted diverse effects on the HMGB1 and HSP70/90 evacuation in NDV/FMW-infected prostate cancer cells. Moreover, ICD markers induced in prostate cancer cells upon NDV/FMW infection, were enhanced by either treatment with a STAT3 (signal transducer and activator of transcription 3) inhibitor or shRNA-mediated knockdown of STAT3. In nude mice bearing prostate cancer cell-derived tumours, the tumours injected with the supernatants of NDV/FMW-infected cells grew smaller than mock-treated tumours. These results indicate that oncolytic NDV provokes the expression of ICD makers in prostate cancer cells. Our data also suggest that a combination of inhibition of STAT3 with oncolytic NDV could boost NDV-based anti-tumour effects against prostate cancer.
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http://dx.doi.org/10.1111/jcmm.15089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171322PMC
April 2020

Key candidate genes of STAT1 and CXCL10 in melanoma identified by integrated bioinformatical analysis.

IUBMB Life 2019 10 19;71(10):1634-1644. Epub 2019 Jun 19.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

The underlying mechanisms and gene signatures of melanoma are unknown. In this study, three expression profile data sets (GSE65568, GSE100050, GSE114445) were integrated to identify candidate genes explaining the pathways and functions of melanoma. Expression data sets including 24 melanoma tumours and 13 normal skin samples were merged and analysed in detail. The three GSE profiles shared 431 differentially expressed genes (DEGs), including 227 upregulated genes, 200 downregulated genes and 4 differentially regulated genes. Moreover, the functions and signalling pathways of the shared DEGs with significant p-values were identified. The two most significant modules were filtered from the DEGs protein-protein interaction (PPI) network, which consisted of 284 nodes. We also plotted the prognostic value of hub genes from an online database. In summary, using integrated bioinformatic analysis, we have identified candidate DEGs and pathways in melanoma that could improve our understanding of the causes and underlying molecular events of melanoma, and these candidate genes and pathways could be therapeutic targets for melanoma.
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http://dx.doi.org/10.1002/iub.2103DOI Listing
October 2019

STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells.

Front Oncol 2019 29;9:436. Epub 2019 May 29.

Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University, Shanghai, China.

Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated. Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors. Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth. Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response.
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http://dx.doi.org/10.3389/fonc.2019.00436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548873PMC
May 2019

Combination of 2- and 3-dimensional contrast-enhanced transvaginal sonography for diagnosis of small adnexal masses.

J Ultrasound Med 2014 Nov;33(11):1889-99

Departments of Ultrasonography (R.H., H.X., Y.F., L.G., H.L.) and Echocardiography (Y.M.), First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Objectives: The purpose of this study was to evaluate the efficacy of the combination of 2-dimensional (2D) and 3-dimensional (3D) contrast-enhanced sonography in discriminating between benign and malignant small adnexal masses.

Methods: Selected patients were evaluated with both 2D and 3D contrast-enhanced sonography after conventional sonography before undergoing any surgery. Time-intensity curves for 2D contrast-enhanced sonography were constructed by using contrast-enhanced sonographic software. A vascular perfusion characteristic analysis was achieved by 2D and 3D contrast-enhanced sonography. Results were finally verified by surgery.

Results: Forty-seven cases of benign and 10 cases of malignant small adnexal masses were discovered. Significant differences in perfusion patterns, time-intensity curve shapes for 2D contrast-enhanced sonography, grayscale contrast-enhanced sonography, and blood flow imaging on 3D contrast-enhanced sonography were observed between benign and malignant masses (P< .05). Two-dimensional contrast-enhanced sonography, 3D contrast-enhanced sonography, parallel combination of 2D and 3D contrast-enhanced sonography, and serial combination of 2D and 3D contrast-enhanced sonography all reached diagnostic sensitivity of 100% for discriminating benign from malignant masses, whereas specificity values were 61.7%, 63.8%, 68.1%, and 57.4%, respectively. Areas under the receiver operating characteristic curves were 0.809, 0.819, 0.840, and 0.787.

Conclusions: Two-dimensional contrast-enhanced sonography is of high value in distinguishing malignant from benign small adnexal masses; 3D contrast-enhanced sonography provides richer and more useful information for evaluation of these masses. Diagnostic sensitivity of 100% can be achieved when using a serial combination of 2D and 3D contrast-enhanced sonography, although specificity needs further improvement.
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http://dx.doi.org/10.7863/ultra.33.11.1889DOI Listing
November 2014
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