Jing-Yuan Fang

Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

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Publications (130)534.77 Total impact

  • Ye Hu · Haiying Tian · Jie Xu · Jing-Yuan Fang
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    ABSTRACT: Long noncoding RNA (lncRNA) is >200 nucleotides long and lacks coding ability. LncRNA was regarded as transcript noise, until emerging results showed its roles in development, homeostasis and carcinogenesis. LncRNAs containing microRNA (miRNA) response elements could compete with the miRNA target gene and regulate its expression through decreasing free functional miRNA. Such lncRNA is called competing endogenous RNA (ceRNA), and the 'lncRNA-miRNA' interaction appreciably enriches the world of RNA-RNA regulation. Gastric cancer involves dysregulation of both protein-coding genes and noncoding genes, and the ceRNA regulatory mechanism may participate in this pathogenic process. In this review, we discuss recent findings on the roles of ceRNAs in gastric carcinogenesis.
    Briefings in functional genomics 09/2015; DOI:10.1093/bfgp/elv036 · 3.67 Impact Factor
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    ABSTRACT: Background: Accumulating evidence links colorectal cancer (CRC) with the intestinal microbiota. However, the disturbance of intestinal microbiota and the role of Fusobacterium nucleatum during the colorectal adenoma-carcinoma sequence have not yet been evaluated. Methods: 454 FLX pyrosequencing was used to evaluate the disturbance of intestinal microbiota during the adenoma-carcinoma sequence pathway of CRC. Intestinal microbiota and mucosa tumor-immune cytokines were detected in mice after introducing 1,2-dimethylhydrazine (DMH), F. nucleatum or Berberine (BBR), using pyrosequencing and Bio-Plex Pro™ cytokine assays, respectively. Protein expressions were detected by western blotting. Results: The levels of opportunistic pathogens, such as Fusobacterium, Streptococcus and Enterococcus spp. gradually increased during the colorectal adenoma-carcinoma sequence in human fecal and mucosal samples. F. nucleatum treatment significantly altered lumen microbial structures, with increased Tenericutes and Verrucomicrobia (opportunistic pathogens) (P < 0.05 = in wild-type C57BL/6 and mice with DMH treatment). BBR intervention reversed the F. nucleatum-mediated increase in opportunistic pathogens, and the secretion of IL-21/22/31, CD40L and the expression of p-STAT3, p-STAT5 and p-ERK1/2 in mice, compared with mice fed with F. nucleatum alone. Conclusions: F. nucleatum colonization in the intestine may prompt colorectal tumorigenesis. BBR could rescue F. nucleatum-induced colorectal tumorigenesis by modulating the tumor microenvironment and blocking the activation of tumorigenesis-related pathways.
    Oncotarget 09/2015; DOI:10.18632/oncotarget.5166 · 6.36 Impact Factor
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    ABSTRACT: Aims: To investigate the antitumor effects of probiotics Clostridium butyricum and Bacillus subtilis on colorectal cancer (CRC) progression. Materials & methods: The effects of C. butyricum and B. subtilis on CRC cells were studied. Male C57BL/6 mice with 1,2-dimethylhydrazine dihydrochloride (DMH)-induced CRC were intervened by these two probiotics and the antitumor effects were examined by comparing the tumor incidence and detecting the inflammatory and immune-related markers. Results & conclusions: C. butyricum and B. subtilis inhibited the proliferation of CRC cells, caused cell cycle arrest and promoted apoptosis. In vivo, these two probiotics inhibited the development of DMH-induced CRC. The molecular mechanism involved reduced inflammation and improved immune homeostasis. This work establishes a basis for the protective role of probiotics B. subtilis and C. butyricum in intestinal tumorigenesis.
    Future Microbiology 09/2015; DOI:10.2217/fmb.15.66 · 4.28 Impact Factor
  • Ping Chen · Yun Cui · Qing-Yan Fu · You-Yong Lu · Jing-Yuan Fang · Xiao-Yu Chen
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    ABSTRACT: Gastric cancer is a typical type of inflammation-related tumor. p42.3 gene highly expresses in gastric cancer but whether it is associated with gastritis is still unknown. Here we will explore the relationship between inflammation and p42.3 gene. Normal gastric epithelium cells (GES-1) were treated with H. pylori and tumor necrosis factor alpha (TNF-α) separately. Total cell mRNA and protein were collected and PCR and western blotting were conducted to determine the relative expression of p42.3 gene. 291 chronic non-atrophic gastritis tissue samples were collected and immunohistochemistry method was used to measure the rate of p42.3 protein expression. The associations between p42.3 protein and the clinicopathological characteristics of patients with chronic non-atrophic gastritis were analyzed. H. pylori can significantly enhance the p42.3 protein expression in GES-1 cells. Moreover, inflammatory cytokines TNF-α can stimulate the p42.3 gene expression in GES-1 cells and further the effect showed a time and dose dependent manner. In addition, the p42.3 gene expression was positively associated with the gastric mucosa inflammation degree and H. pylori infection (P = 0.000). Its expression rate was significantly high in gastric mucosa with severe inflammation and in H. pylori infection cases. The p42.3 gene expression is associated with the gastric mucosa inflammation and it can be stimulated by TNF-α and H. pylori respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Digestive Diseases 08/2015; DOI:10.1111/1751-2980.12282 · 1.96 Impact Factor
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    Lunxi Liang · Luoyan Ai · Jin Qian · Jing-Yuan Fang · Jie Xu
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    ABSTRACT: The gut microbiota is commonly referred to as a hidden organ due to its pivotal effects on host physiology, metabolism, nutrition and immunity. The gut microbes may be shaped by environmental and host genetic factors, and previous studies have focused on the roles of protein-coding genes. Here we show a link between long non-coding RNA (lncRNA) expression and gut microbes. By repurposing exon microarrays and comparing the lncRNA expression profiles between germ-free, conventional and different gnotobiotic mice, we revealed subgroups of lncRNAs that were specifically enriched in each condition. A nearest shrunken centroid methodology was applied to obtain lncRNA-based signatures to identify mice in different conditions. The lncRNA-based prediction model successfully identified different gnotobiotic mice from conventional and germ-free mice, and also discriminated mice harboring transplanted microbes from fecal samples of mice or zebra fishes. To achieve optimal prediction accuracy, fewer lncRNAs were required in the prediction model than protein-coding genes. Taken together, our study demonstrated the effecacy of lncRNA expression profiles in discriminating the types of microbes in the gut. These results also provide a resource of gut microbe-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs in host-microbes interactions.
    Scientific Reports 06/2015; 5:11763. DOI:10.1038/srep11763 · 5.58 Impact Factor
  • Hui-Min Chen · Jing-Yuan Fang
    05/2015; 1(4):201-208. DOI:10.1159/000380784
  • Ya-Nan Yu · Jing-Yuan Fang
    05/2015; 2(1):26-32. DOI:10.1159/000380892
  • Yanan Yu · Zibin Tian · Tachung Yu · Jie Hong · Jing-Yuan Fang
    Gastroenterology 04/2015; 148(4):S-371-S-372. DOI:10.1016/S0016-5085(15)31245-2 · 16.72 Impact Factor
  • Jin Qian · Jie Xu · Jing-Yuan Fang
    Gastroenterology 04/2015; 148(4):S-103-S-104. DOI:10.1016/S0016-5085(15)30357-7 · 16.72 Impact Factor
  • Lin-Lin Ren · Jie Hong · Haoyan Chen · Jing-Yuan Fang
    Gastroenterology 04/2015; 148(4):S-374. DOI:10.1016/S0016-5085(15)31255-5 · 16.72 Impact Factor
  • Tian-Tian Sun · Haoyan Chen · Jie Hong · Jing-Yuan Fang
    Gastroenterology 04/2015; 148(4):S-564. DOI:10.1016/S0016-5085(15)31900-4 · 16.72 Impact Factor
  • Jie Xu · Ye Hu · Jing-Yuan Fang
    Gastroenterology 04/2015; 148(4):S-570. DOI:10.1016/S0016-5085(15)31924-7 · 16.72 Impact Factor
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    ABSTRACT: Members of the inositol phosphate metabolism pathway regulate cell proliferation, migration and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and are frequently dysregulated in cancer. Whether germline genetic variants in inositol phosphate metabolism pathway are associated with cancer risk remains to be clarified. We examined the association between inositol phosphate metabolism pathway genes and risk of eight types of cancer using data from genome-wide association studies. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-based associations were tested using the permutation-based adaptive rank-truncated product method. The overall inositol phosphate metabolism pathway was significantly associated with risk of lung cancer (P = 2.00 × 10(-4)), esophageal squamous cell carcinoma (P = 5.70 × 10(-3)), gastric cancer (P = 3.03 × 10(-2)) and renal cell carcinoma (P = 1.26 × 10(-2)), but not with pancreatic cancer (P = 1.40 × 10(-1)), breast cancer (P = 3.03 × 10(-1)), prostate cancer (P = 4.51 × 10(-1)), and bladder cancer (P = 6.30 × 10(-1)). Our results provide a link between inherited variation in the overall inositol phosphate metabolism pathway and several individual genes and cancer. Further studies will be needed to validate these positive findings, and to explore its mechanisms.
    Scientific Reports 02/2015; 5:8473. DOI:10.1038/srep08473 · 5.58 Impact Factor
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    ABSTRACT: Since observational data in the urban residents are required to better assess the risk factors of colorectal neoplasm occurrence and the effectiveness of colonoscopy screening and surveillance, we conducted a case-control study at multicenters in China to identify patient characteristics and neoplasm features of colorectal adenoma (CRA) and colorectal carcinoma (CRC). A total of 4089 patients who had undergone a colonoscopy from 19 hospitals were enrolled, of which 1106 had CRA and 466 had CRC. They were compared with controls. The analysis provides features and risk factors of colorectal neoplasm using multivariate logistic regression. Increasing age, a family history of colorectal cancer or previous cases of colorectal adenoma or hypertension disease, gastrointestinal surgery, regular intake of pickled food (adjusted odds ratio [aOR] 1.42, 95 % confidence interval [CI], 1.048-1.924), consumption of alcohol, and a positive result of fecal occult blood testing (FOBT; aOR 2.509, 95 % CI 1.485-4.237) were associated with an increased risk of CRA. In the CRC group, increasing age, regular intake of pickled foods, and a positive FOBT result were risk factors. In addition, a positive abdominal computed tomography (CT) before a colonoscopy and physical signs of emaciation were also significantly associated with an increasing risk of colorectal carcinoma. Regular intake of vegetables decreased the risk of both CRA and CRC. Age, pickled foods, and a positive FOBT are risk factors for colorectal neoplasm. Vegetable intake was associated with a decreased risk of CRA and CRC.
    International Journal of Colorectal Disease 12/2014; 30(3). DOI:10.1007/s00384-014-2090-9 · 2.45 Impact Factor
  • Haoyan Chen · Jie Xu · Jie Hong · Ruqi Tang · Xi Zhang · Jing-Yuan Fang
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    ABSTRACT: Colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behavior and response to therapy. Increasing evidence suggests that long noncoding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, and some of them have been implicated in CRC biogenesis and prognosis. Using an lncRNA-mining approach, we constructed lncRNAs expression profiles in approximately 888 CRC samples. By applying unsupervised consensus clustering to LncRNA expression profiles, we identified five distinct molecular subtypes of CRC with different biological pathways and phenotypically distinct in their clinical outcome in both univariate and multivariate analysis. The prognostic significance of the lncRNA-based classifier was confirmed in independent patient cohorts. Further analysis revealed that most of the signature lncRNAs positively correlated with somatic copy number alterations (SCNAs). This lncRNAs-based classification schema thus provides a molecular classification applicable to individual tumors that has implications to influence treatment decisions.
    Molecular Oncology 12/2014; 8(8). DOI:10.1016/j.molonc.2014.05.010 · 5.33 Impact Factor
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    ABSTRACT: It is increasingly evident that long non-coding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer (GC), termed GAPLINC, based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human GC specimens. GAPLINC is a 924-bp long lncRNA that is highly expressed in GC tissues. GAPLINC suppression and with gene expression profiling in GC cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of GC patients with very poor survival. Taken together, our results identify a non-coding regulatory pathway for the CD44 oncogene, shedding new light on the basis for GC cell invasiveness.
    Cancer Research 10/2014; 74(23). DOI:10.1158/0008-5472.CAN-14-0686 · 9.33 Impact Factor
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    ABSTRACT: Recent studies have increasingly linked microRNAs to colorectal cancer (CRC). MiR-194 has been reported deregulated in different tumor types, whereas the function of miR-194 in CRC largely remains unexplored. Here we investigated the biological effects, mechanisms and clinical significance of miR-194. Functional assay revealed that overexpression of miR-194 inhibited CRC cell viability and invasion in vitro and suppressed CRC xenograft tumor growth in vivo. Conversely, block of miR-194 in APC(Min/+) mice promoted tumor growth. Furthermore, miR-194 reduced the expression of AKT2 both in vitro and in vivo. Clinically, the expression of miR-194 gradually decreased from 20 normal colorectal mucosa (N-N) cases through 40 colorectal adenomas (CRA) cases and then to 40 CRC cases, and was negatively correlated with AKT2 and pAKT2 expression. Furthermore, expression of miR-194 in stool samples was gradually decreased from 20 healthy cases, 20 CRA cases, then to 28 CRC cases. Low expression of miR-194 in CRC tissues was associated with large tumor size (P=0.006), lymph node metastasis (P=0.012) and shorter survival (HR =2.349, 95% CI = 1.242 to 4.442; P=0.009). In conclusion, our data indicated that miR-194 acted as a tumor suppressor in the colorectal carcinogenesis via targeting PDK1/AKT2/XIAP pathway, and could be a significant diagnostic and prognostic biomarker for CRC.
    Theranostics 09/2014; 4(12):1193-208. DOI:10.7150/thno.8712 · 8.02 Impact Factor
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    ABSTRACT: In this study we investigated the biological role and mechanism of miR-198 in colorectal carcinoma (CRC). MiR-198 expression was shown to exhibit a strongly negative correlation with lymph node invasion, distant metastasis and patient survival in examinations of colorectal cancer tissues and paired normal colorectal mucosa tissues. fucosyl transferase 8 (FUT8) was identified as a potential target of miR-198 in bioinformatics analysis and luciferase reporter assays. Overexpression of miR-198 in CRC cell lines decreased FUT8 levels as shown by immunofluorescence analysis, and inhibited cell proliferation, migration, and invasion. These anti-tumor phenotypes were rescued by reconstitution of FUT8 expression. Furthermore, miR-198 was shown to target the 3'UTR of FUT8 directly to downregulate FUT8 expression at both mRNA and protein levels in qRT-PCR and Western blot analyses, respectively. In vivo, restoration of miR-198 significantly inhibited xenograft growth and invasion of CRC tumors in nude mice. Therefore, it could be concluded that miR-198 suppresses the proliferation and invasion of CRC by directly targeting FUT8.
    Scientific Reports 09/2014; 4:6145. DOI:10.1038/srep06145 · 5.58 Impact Factor
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    ABSTRACT: The impact of cellular oxidative stress in promoting the epithelial-mesenchymal transition (EMT) has been noticed. Our previous study shows that SENP3, a redox-sensitive SUMO2/3-specific protease, accumulates in a variety of cancers, but whether SENP3 and SUMOylation involve in the regulation of EMT is unclear. The present study uncovers a novel role of SENP3 in promoting the EMT process in gastric cancer via regulating an EMT-inducing transcription factor, forkhead box C2 (FOXC2). We demonstrate that the expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells. A nude mouse model and a set of patient's specimens suggest the correlation between SENP3 and gastric cancer metastasis. Biochemical assays identify FOXC2 as a substrate of SENP3. Meanwhile N-cadherin is verified as a target gene of FOXC2, which is transcriptionally activated by a SUMO-less FOXC2. Additionally, reactive oxygen species-induced de-SUMOylation of FOXC2 can be blocked by silencing endogenous SENP3. In conclusion, SENP3, which is increased in gastric cancer cells, potentiates the transcriptional activity of FOXC2 through de-SUMOylation, in favor of the induction of specific mesenchymal gene expression in gastric cancer metastasis.
    Oncotarget 08/2014; 5(16):7093-7104. DOI:10.18632/oncotarget.2197 · 6.36 Impact Factor
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    ABSTRACT: Covalent modification adding acetyl groups to the C terminus of the p53 protein has been suggested to be required for its functional activation as a tumour suppressor. However, it remains largely unknown how p53 acetylation is deregulated in colorectal cancer (CRC), which is the third most commonly diagnosed cancer worldwide. Here we show that ArhGAP30, a Rho GTPase-activating protein, is a pivotal regulator for p53 acetylation and functional activation in CRC. ArhGAP30 binds to p53 C-terminal domain and P300, facilitating P300-mediated acetylation of p53 at lysine 382. ArhGAP30 expression is required for p53 activation upon DNA damage stress, and the level of ArhGAP30 correlates with p53 acetylation and functional activation in CRC tissues. Moreover, low level of ArhGAP30 expression associates with poor survival of CRC patients. In summary, ArhGAP30 is required for p53 acetylation and functional activation in CRC, and the expression of ArhGAP30 is a potential prognostic marker for CRC.
    Nature Communications 08/2014; 5:4735. DOI:10.1038/ncomms5735 · 11.47 Impact Factor

Publication Stats

1k Citations
534.77 Total Impact Points


  • 2009–2015
    • Shanghai Jiao Tong University
      • • Department of Gastroenterology and Hepatology (Renji)
      • • Institute of Digestive Disease
      • • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2002–2014
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2008–2013
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China