Publications by authors named "Jiuming Li"

11 Publications

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SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop.

J Exp Clin Cancer Res 2021 Nov 15;40(1):360. Epub 2021 Nov 15.

Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, 214062, Jiangsu, China.

Background: Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear.

Methods: SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC.

Results: Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop.

Conclusions: We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.
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http://dx.doi.org/10.1186/s13046-021-02162-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591805PMC
November 2021

Nanobody-Engineered Natural Killer Cell Conjugates for Solid Tumor Adoptive Immunotherapy.

Small 2021 Nov 15;17(45):e2103463. Epub 2021 Oct 15.

Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, P. R. China.

Cancer immunotherapy based on natural killer (NK) cells is demonstrated to be a promising strategy. However, NK cells are deficient in ligands that target specific tumors, resulting in limited antitumor efficacy. Here, a glycoengineering approach to imitate the chimeric antigen receptor strategy and decorate NK cells with nanobodies to promote NK-based immunotherapy in solid tumors is proposed. Nanobody 7D12, which specifically recognizes the human epidermal growth factor receptor (EGFR) that is overexpressed on many solid tumors, is coupled to the chemically synthesized DBCO-PEG -GGG-NH by sortase A-mediated ligation to generate DBCO-7D12. The NK92MI cells bearing azide groups are then equipped with DBCO-7D12 via bioorthogonal click chemistry. The resultant 7D12-NK92MI cells exhibit high specificity and affinity for EGFR-overexpressing tumor cells in vitro and in vivo by the 7D12-EGFR interaction, causing increased cytokine secretion to more effectively kill EGFR-positive tumor cells, but not EGFR-negative cancer cells. Importantly, the 7D12-NK92MI cells also show a wide anticancer spectrum and extensive tumor penetration. Furthermore, mouse experiments reveal that 7D12-NK92MI treatment achieves excellent therapeutic efficacy and outstanding safety. The authors' works provide a cell modification strategy using specific protein ligands without genetic manipulation and present a potential novel method for cancer-targeted immunotherapy by NK cells.
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http://dx.doi.org/10.1002/smll.202103463DOI Listing
November 2021

Immune checkpoint molecule TIGIT manipulates T cell dysfunction in septic patients.

Int Immunopharmacol 2021 Oct 13;101(Pt B):108205. Epub 2021 Oct 13.

Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China. Electronic address:

Sepsis is a dysregulated host response to infection. T cell dysfunction results in the failure to eradicate pathogens and the increased susceptibility to nosocomial infections and mortality during sepsis. Although PD-1 has shown to be a promising target to interfere with T cells dysfunction, the role of other coinhibitory receptors in sepsis remains largely elusive. Here we demonstrated that the immune checkpoint molecule TIGIT on lymphocytes and the critical role of TIGIT in regulating T cell responses in sepsis. Fifty septic patients and seventeen healthy donors were prospectively enrolled. The expression patterns of TIGIT and other molecules on lymphocytes were quantitated by flow cytometry. Ex vivo functional assays were also conducted. Results show that TIGIT expression on T cells was significantly upregulated in sepsis and septic shock patients relative to healthy donors. Elevated frequencies of TIGIT T cells correlated with aggravated inflammatory response and organ injuries. Of note, TIGIT expression on CD8 T cells showed a competitive capability to predict ICU mortality in sepsis. TIGIT T cells expressed higher levels of PD-1, lower levels of CD226, and released fewer cytokines. Strikingly, ex vivo blockade of TIGIT using anti-TIGIT antibody restored the frequencies of cytokine-producing T cells from septic patients. These data illustrate that TIGIT on T cells is being used not only as a clinical predictor of poor prognosis but also as a potential target of novel immunotherapeutic intervention during sepsis.
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http://dx.doi.org/10.1016/j.intimp.2021.108205DOI Listing
October 2021

Long noncoding RNA MCM3AP-AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR-193a-5p/SENP1.

Cancer Med 2021 04 8;10(7):2470-2481. Epub 2021 Mar 8.

Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.

Background: Accumulating evidences have shown that long noncoding RNAs (lncRNAs) play key roles in many diseases, including cancer. Several studies reported that MCM3AP antisense RNA 1 (MCM3AP-AS1) was associated with the tumorigenesis and progression. However, the specific function and mechanism of MCM3AP-AS1 in colorectal cancer (CRC) have not been fully understood.

Methods: The expression of MCM3AP-AS1 was detected by quantitative reverse transcription PCR (RT-qPCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK-8 assay, colony formation assay, transwell assay, xenograft and lung metastasis mouse models were used to examine the tumor-promoting function of MCM3AP-AS1 in vitro and in vivo. The binding relationship between MCM3AP-AS1, miR-193a-5p and sentrin-specific peptidase 1 (SENP1) were screened and identified by databases, RT-qPCR, dual luciferase reporter assay and western blot.

Results: In the present study, we got that the expression of MCM3AP-AS1 was higher in CRC tissues than in paired NCTs, and increased MCM3AP-AS1 expression was associated with adverse outcomes in CRC patients. Functional experiments in vitro revealed that silencing of MCM3AP-AS1 could inhibit the proliferation, colony formation, migratory, and invasive abilities of CRC cells. The mouse models of xenograft and lung metastasis further confirmed that in vivo silencing MCM3AP-AS1 could significantly inhibit the growth and metastasis of CRC. Further mechanism studies indicated that MCM3AP-AS1 could sponge miR-193a-5p and inhibit the activity of it. What is more, SENP1 was proved to be a novel target of miR-193a-5p and could be upregulated by MCM3AP-AS1. At last, we observed that SENP1 overexpression in CRC tissues was closely related to unfavorable prognosis.

Conclusion: Taken together, we identified in CRC the MCM3AP-AS1/miR-193a-5p/SENP1 regulatory axis, which affords a therapeutic possibility for CRC.
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http://dx.doi.org/10.1002/cam4.3830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982620PMC
April 2021

Ternary flower-sphere-like MnO-graphite/reduced graphene oxide nanocomposites for supercapacitor.

Nanotechnology 2021 Apr;32(18):185401

Inner Mongolia Key Laboratory of Carbon Nanomaterials, Nano Innovation Institute (NII), College of Chemistry and Materials Science, Inner Mongolia University for Nationalities (IMUN), Tongliao 028000, People's Republic of China.

Chemical fabrication of a nanocomposite structure for electrode materials to regulate the ion diffusion channels and charge transfer resistances and Faradaic active sites is a versatile strategy towards building a high-performance supercapacitor. Here, a new ternary flower-sphere-like nanocomposite MnO-graphite (MG)/reduced graphene oxide (RGO) was designed using the RGO as a coating for the MG. MnO-graphite (MnO-4) was obtained by KMnO oxidizing the pretreated graphite in an acidic medium (pH = 4). The GO coating was finally reduced by the NaBH to prepare the ternary nanocomposite MG. The microstructures and pore sizes were investigated by x-ray diffraction, scanning electron microscopy, thermogravimetric analysis, and nitrogen adsorption/desorption. The electrochemical properties of MG were systematically investigated by the cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy in NaSO solution. The MG as an electrode material for supercapacitor exhibits a specific capacitance of 478.2 and 454.6 F g at a current density of 1.0 and 10.0 A g, respectively. In addition, the capacitance retention was 90% after 8,000 cycles. The ternary nanocomposite enhanced electrochemical performance originates from the specific flower-sphere-like morphology and coating architecture bringing higher specific surface area and lower charge transfer resistance (R).
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http://dx.doi.org/10.1088/1361-6528/abdb62DOI Listing
April 2021

Case Report: Prostate Adenocarcinoma With Mucinous Features of Normal-Level Serum PSA, Atypical Imaging, Biopsy-Negative, and Peculiar Urethrocystoscopic Manifestation.

Front Oncol 2020 23;10:504381. Epub 2020 Dec 23.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Mucinous tumors of the prostate are seen as rare morphological variants of prostate carcinoma. Misdiagnosis and missed diagnosis are frequent clinically, especially when the clinical performance appears atypical. Furthermore, there has not been reported about the urethrocystoscopic performance of mucinous adenocarcinoma growing into the prostatic urethra so far.

Case Presentation: The current case report describes a 48-year old Asian male who was hospitalized because of intermittent gross hematuria for more than two months. The patient was diagnosed as prostatic space occupying lesions and an examination of needle biopsy was conducted on him, which did not indicate a definite malignancy. Transurethral plasma kinetic resection of the prostate (TUPKP) was performed for the patient, but the postoperative pathology revealed prostatic adenocarcinoma with mucinous features. Specifically, two cord-like neoplasms, extending to the bladder neck, were found through urethrocystoscopy in the prostatic urethra, both of which grew pedicles. The pedicles were situated on the right side of the parenchyma of the prostate. Finally, the patient underwent radical prostatectomy three weeks later.

Conclusion: Here, we reported a case that prostatic adenocarcinoma with mucinous features was diagnosed after TUPKP. The patient had normal serum prostate-specific antigen levels with atypical images and negative biopsy result. This report lays stress on the vigilance of clinicians in prostate mucinous adenocarcinoma and makes a description of its peculiar urethrocystoscopic manifestation, typical imaging, and unique growth pattern for the first time.
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http://dx.doi.org/10.3389/fonc.2020.504381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786235PMC
December 2020

Sam68 promotes aerobic glycolysis in colorectal cancer by regulating PKM2 alternative splicing.

Ann Transl Med 2020 Apr;8(7):459

Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, China.

Background: Sam68, an RNA-binding protein, exerts oncogenic functions in several types of cancer. However, the specific functions and mechanisms of Sam68 in colorectal cancer (CRC) had not been previously clarified. Pyruvate kinase muscle (PKM)2 is the key rate-limiting enzyme in glycolysis, and PKM2 maintains the glycolysis-dominant energy metabolism in most cancer cells.

Methods: CCK8 assay was performed to show the effect of Sam68 on cell growth. Pyruvate kinase activity and lactate detection assays were performed to analyze the effects of Sam68 on aerobic glycolysis. RNA immunoprecipitation (RIP) was used to detect the binding of Sam68 to the sequence. Western blot and real-time PCR were executed to analyze the regulation of by Sam68.

Results: Gain-of-function and loss-of-function studies showed that ectopic expression of Sam68 promoted glycolysis and cell proliferation in CRC cells, whereas Sam68 knockdown inhibited glycolysis and cell proliferation. Mechanically, Sam68 modulated the expression profile of pyruvate kinase (PKM2 or PKM1) by regulating its alternative splicing. Overexpression of Sam68 was associated with decreased / ratio, which positively contributed to the glycolysis procedure. Sam68 significantly promoted cell proliferation and caused a decrease of / ratio, resulting in the metabolism of glucose switched from oxidative phosphorylation to glycolysis in CRC cells. Besides, Sam68 enhanced mRNA transport from the nucleus to cytoplasm and increased the expression of PKM2 protein, resulting in elevated pyruvate kinase activity and lactate production.

Conclusions: These findings suggested that Sam68 affected cell growth and glycolysis pathway by regulating the alternative splicing and expression of PKM2 in CRC.
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http://dx.doi.org/10.21037/atm.2020.03.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210197PMC
April 2020

Role of the functional variant (-652T>G) in the XRCC4 promoter in prostate cancer.

Mol Biol Rep 2014 Nov 6;41(11):7463-70. Epub 2014 Aug 6.

Department of Urology, Second People's Hospital of Wuxi Affiliated to Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China.

Several genes encoding DNA repair molecules have been proposed as cancer-susceptibility genes. Many studies have suggested that SNPs in XRCC4 could be implicated in altering the risk of prostate cancer (PCa). We examined the role of the functional variant (-652T>G) in the XRCC4 promoter in PCa. The transcriptional activity of XRCC4 gene was measured by luciferase assay. We performed real-time PCR/immunohistochemical assay to verify the association between expression level of XRCC4 mRNA/protein and XRCC4 -652T>G polymorphism. In addition, electrophoretic mobility shift assay (EMSA) was used to confirm whether this polymorphism has an effect on binding ability of the transcription factor. We found that the G variant significantly increased the transcription activity of the XRCC4 gene and the binding ability of transcriptional factor GATA-1 to the XRCC4 promoter. Furthermore, the results suggested that the XRCC4 protein and mRNA were overexpressed in individuals who carried the -652G allele compared to carriers of the -652T allele. In addition, the expression of XRCC4 in PCa tissues was lower than in adjacent normal tissues. Our data suggest that the XRCC4 promoter -652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. Case-control studies are required to validate our findings in the future.
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http://dx.doi.org/10.1007/s11033-014-3636-1DOI Listing
November 2014

Preparation and antibacterial property of silver-containing mesoporous 58S bioactive glass.

Mater Sci Eng C Mater Biol Appl 2014 Sep 11;42:22-30. Epub 2014 May 11.

The Quartermaster Research Institute of the General Logistic Department of CPLA, Beijing 100082, China.

The modified mesoporous 58S bioglass (SM58S) was prepared through surface modification of the mesoporous 58S bioglass (M58S) with γ-aminopropyl triethoxysilane (KH550). The results of Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) showed that the amino groups were grafted to the surface of M58S after modification with KH550. The silver-containing SM58S (Ag-SM58S) and M58S (Ag-M58S) were prepared by the dipping method. The Ag(+) loading capacity, release rate and antibacterial properties of Ag-SM58S and Ag-M58S were investigated. It is indicated that surface modification of M58S with KH550 can improve the Ag(+) loading capacity. The result of antibacterial property showed that Ag-SM58S exhibited significant anti-bacterial effects against Escherichia coli and Staphylococcus aureus. The sustained release of Ag(+) from Ag-SM58S for 768h ensured excellent antibacterial property of Ag-SM58S. In vitro osteoblast proliferation and differentiation tests showed that Ag-SM58S was a good matrix for the growth of osteoblasts. Consequently, the results of the study suggested that Ag-SM58S might be a promising bone repair material.
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http://dx.doi.org/10.1016/j.msec.2014.05.004DOI Listing
September 2014

A novel integrated biosensor based on co-immobilizing the mediator and microorganism for water biotoxicity assay.

Analyst 2014 Jun;139(11):2806-12

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

A novel integrated biosensor for biotoxicity assay has been developed by co-immobilizing microorganisms and mediators within a novel redox hydrogel. The proposed redox hydrogel acts as an immobilizing matrix both for microorganism E. coli and redox mediator, which was prepared by grafting the benzoquinone (BQ) redox mediator with gelatin/silica hybrid hydrogel (GSH). This redox hydrogel was characterized by UV-Vis, CV and EIS. The feasibility of the novel integrated biosensor for biotoxicity assay was demonstrated by measuring the heavy metal ions Hg(2+), Cu(2+) and Cd(2+) polluted water as the model toxicants. The results showed that the integrated biosensor was able to evaluate the water biotoxicity and the corresponding 50% inhibiting concentrations (IC50) are determined to be 21.2 μg mL(-1), 44 μg mL(-1) and 79 μg mL(-1), respectively. This integrated biosensor could achieve real-time monitoring of water quality and evaluation of biotoxicity. Moreover it avoids the waste and contamination of mediators, and also simplifies the assay process.
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http://dx.doi.org/10.1039/c4an00243aDOI Listing
June 2014

A functional polymorphism in MSMB gene promoter is associated with prostate cancer risk and serum MSMB expression.

Prostate 2010 Jul;70(10):1146-52

Department of Urology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.

Background: To explore the reported association of SNP marker rs10993994 with prostate cancer identified by two independent in two genome-wide association studies (GWAS) further, we performed a case-control study in southern Chinese Han population. Consequently, we detected the serum levels of MSMB expression with different genotypes in the cases and controls to characterize the functional consequences of rs10993994.

Materials And Methods: Two hundred fifty-one prostate cancer and 258 control subjects were included in the cancer association study and 90 serum samples were used to test the expression of the MSMB by Enzyme-linked immunosorbent assay (ELISA).

Results: We found that the T allele displayed an increased prevalence of prostate cancer compared with the C allele (OR = 1.30, 95% CI = 1.01-1.67, P = 0.040). Moreover, the prostate cancer patients carrying CT/TT genotype had significantly decreased serum MSMB levels compared to those with CC genotype (16.32 +/- 3.98 microg/L vs. 19.33 +/- 4.27 microg/L, P = 0.022).

Conclusions: rs10993994 in MSMB promoter affects serum MSMB expression, contributes to the genetic predisposition to prostate cancer in southern Chinese Han population.
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http://dx.doi.org/10.1002/pros.21149DOI Listing
July 2010
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