LncRNA KIAA0087 suppresses the progression of osteosarcoma by mediating the SOCS1/JAK2/STAT3 signaling pathway

Gong Haoli,Tao Ye,Xiao Sheng,Li Xin,Fang Ke,Wen Jie,He Pan,Zeng Ming 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Long noncoding RNAs (lncRNAs), widely expressed in mammalian cells, play pivotal roles in osteosarcoma (OS) progression. Nevertheless, the detailed molecular mechanisms of lncRNA KIAA0087 in OS remain obscure. Here, the roles of KIAA0087 in OS tumorigenesis were investigated. KIAA0087 and miR-411-3p levels were detected by RT-qPCR. Malignant properties were assessed by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. SOCS1, EMT, and JAK2/STAT3 pathway-related protein levels were measured by western blotting. Direct binding between miR-411-3p and KIAA0087/SOCS1 was validated by a dual-luciferase reporter, RIP, and FISH assays. In vivo growth and lung metastasis were evaluated in nude mice. The expression levels of SOCS1, Ki-67, E-cadherin, and N-cadherin in tumor tissues were measured by immunohistochemical staining. Downregulation of KIAA0087 and SOCS1 and upregulation of miR-411-3p were found in OS tissues and cells. Low expression of KIAA0087 was associated with a poor survival rate. Forced expression of KIAA0087 or miR-411-3p inhibition repressed the growth, migration, invasion, EMT, and activation of the JAK2/STAT3 pathway and triggered apoptosis of OS cells. However, the opposite results were found with KIAA0087 knockdown or miR-411-3p overexpression. Mechanistic experiments indicated that KIAA0087 enhanced SOCS1 expression to inactivate the JAK2/STAT3 pathway by sponging miR-411-3p. Rescue experiments revealed that the antitumor effects of KIAA0087 overexpression or miR-411-3p suppression were counteracted by miR-411-3p mimics or SOCS1 inhibition, respectively. Finally, in vivo tumor growth and lung metastasis were inhibited in KIAA0087-overexpressing or miR-411-3p-inhibited OS cells. In summary, the downregulation of KIAA0087 promotes the growth, metastasis, and EMT of OS by targeting the miR-411-3p-mediated SOCS1/JAK2/STAT3 pathway.

Single Nucleotide Polymorphisms of NLRP12 Gene and Association with Non-specific Digestive Disorder in Rabbit

Liu, Yun-Fu,Zhang, Gong-Wei,Xiao, Zheng-Long,Yang, Yu,Deng, Xiao-Song,Chen, Shi-Yi,Wang, Jie,Lai, Song-Jia Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.8

The NLRP12 (NLR family, pyrin domain containing 12) serves as a suppressor factor in the inflammatory response and protects the host against inflammation-induced damage. In the present study, we aimed to study the polymorphisms of NLRP12 gene and its association with susceptibility to non-specific digestive disorder (NSDD) in rabbits. We re-sequenced the entire coding region of the rabbit NLRP12 gene and detected a total of 19 SNPs containing 14 synonymous and five non-synonymous variations. Among them, the coding SNP (c.1682A>G), which would carry a potential functional implication, was subsequently subjected to genotyping for case-control association study (272 cases and 267 controls). The results revealed that allele A was significantly protective against NSDD with an odds ratio value of 0.884 (95% confidence interval, 0.788 to 0.993; p = 0.038). We also experimentally induced NSDD in growing rabbits by feeding a fibre-deficient diet and subsequently investigated NLRP12 mRNA expression. The mRNA expression of NLRP12 in healthy status was significantly higher than that in severe NSDD (p = 0.0016). The highest expression was observed in individuals carrying the protective genotype AA (p = 0.0108). These results suggested that NLRP12 was significantly associated with the NSDD in rabbits. However, the precise molecular mechanism of NLRP12 involving in the development of rabbit NSDD requires further research.

Antioxidant Activities of Novel Small-molecule Polysaccharide Fractions Purified from Portulaca oleracea L.

Yuping Li,Li-Hua Yao,Guan-Jie Wu,Xiao-Fang Pi,Yan-Chun Gong,Ruo-Shong Ye,Chen-Xi Wang 한국식품과학회 2014 Food Science and Biotechnology Vol.23 No.6

Novel small-molecule polysaccharide fractions,named POP II and POP III, were purified from Portulacaoleracea L. with average Mw values of 9.25 and 8.03 kDa,respectively. Monosaccharide analysis revealed that POP IIwas composed of Rha, Ara, Man, Glc, and Gal with molarratios of 1: 1.42: 0.44: 0.88: 1.59. POP III was composedof Rha, Ara, Glc, and Gal with molar ratios of 1: 1.16:0.23: 0.59. The antioxidant activities of the fractions wereevaluated using cell-free and cell-mediated radical generatingsystems. POPII and POP III possessed strong antioxidantactivities in both systems. The 2 novel polysaccharidefractions extracted from P. oleracea L. can be developed asnatural antioxidants for treatment of free radical-relateddiseases.

Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma

Li Xun,Zhang Cheng-Cheng,Lin Xiao-Tong,Zhang Jie,Zhang Yu-Jun,Yu Hong-Qiang,Liu Ze-Yu,Gong Yi,Zhang Lei-Da,Xie Chuan-Ming 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Dysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.

The complete mitochondrial genome sequence of the little grebe (Tachybaptus ruficollis)

Mei-dong Jing,Ling Huang,Yi-cheng Wang,Yi Zou,Xiao-min Sun,Jie Gong 한국유전학회 2017 Genes & Genomics Vol.39 No.1

Podicipediformes comprises one family (Podicipedidae) including 6 genera, 22 species, and the phylogenetic placement of this order was still in debate. In this study, we sequenced the complete mitochondrial genome (mitogenome) of little grebe (Tachybaptus ruficollis) in Podicipediformes, and explored the phylogenetic position of this order with mitogenome sequences of 21 species from ten families in seven orders. The genome was 16,688 bp in length, and contained 37 genes typical to avian mitogenomes and one control region. The gene organization and characters were similar with other two mitogenomes available in Podicipediformes to date. Phylogenetic tree was constructed with Bayesian method based on mitogenome sequences excluding the control regions. The results supported the closest relationship between Podicipediformes and Phoenicopteriformes, and the topology of our tree was generally similar with the conclusions of previous molecular systematic investigations. Our results furtherly proved the validity of mitogenome data in taxonomic and phylogenetic studies.

Six new dammarane-type triterpene saponins from Panax ginseng flower buds and their cytotoxicity

Li, Ke-Ke,Li, Sha-Sha,Xu, Fei,Gong, Xiao-Jie The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

Background: Panax ginseng has been used for a variety of medical purposes in eastern countries for more than two thousand years. From the extensive experiences accumulated in its long medication use history and the substantial strong evidence in modern research studies, we know that ginseng has various pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascular system-protective effects. The active chemical constituents of ginseng, ginsenosides, are rich in structural diversity and exhibit a wide range of biological activities. Methods: Ginsenoside constituents from P. ginseng flower buds were isolated and purified by various chromatographic methods, and their structures were identified by spectroscopic analysis and comparison with the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide method was used to test their cytotoxic effects on three human cancer cell lines. Results: Six ginsenosides, namely 6'-malonyl formyl ginsenoside F₁ (1), 3β-acetoxyl ginsenoside F₁ (2), ginsenoside Rh₂₄ (6), ginsenoside Rh₂₅ (7), 7β-hydroxyl ginsenoside Rd (8) and ginsenoside Rh₂₆ (10) were isolated and elucidated as new compounds, together with four known compounds (3-5 and 9). In addition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values, a tentative structure-activity relationship was also discussed based on the results of our bioassay. Conclusion: The study of chemical constituents was useful for the quality control of P. ginseng flower buds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxic activities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51 and 20.48 μM, respectively.

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Li, Qing-Qing,Lu, Zhi-Hao,Yang, Li,Lu, Ming,Zhang, Xiao-Tian,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Expression of Endogenous Hypoxia Markers in Vulvar Squamous Cell Carcinoma

Li, Yu-Zhu,Li, Shu-Ling,Li, Xia,Wang, Li-Jie,Wang, Jiu-Ling,Xu, Jia-Wen,Wu, Zhi-Hong,Gong, Li,Zhang, Xiao-Dan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-$1{\alpha}$ expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-$1{\alpha}$, GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC.

Association of IgE-mediated allergen sensitivity and promoter polymorphisms of chemokine (C–C motif) ligand 5 gene in Han Chinese patients with allergic skin diseases

Ji-Chang Zhou,Yu-Mei Zhu,Zheng Chen,Shan He,Shi-jie Zheng,Jun-luan Mo,Xiao-Li Liu,Chun-mei Gong,Bin Hou,Hui Yang 한국유전학회 2015 Genes & Genomics Vol.37 No.5

Two single nucleotide polymorphisms (SNPs), rs2280788 (-28C[G) and rs2107538 (-403G[A), in the promoter region of chemokine (C–C motif) ligand 5 (CCL5) was reported to be involved in the immunoglobulin E (IgE) expression and IgE-mediated allergic reactions. This study was to investigate the characteristics of total serum IgE level, specific allergen sensitivities and the two SNPs in the allergic skin disease (ASD) patients. ASD patients visiting the dermatological outpatient department of a local hospital were included with certain criteria, and the fasting venous blood was sampled for analysis. Total serum IgE was assayed with an ELISA kit, and 14 kinds of allergen-specific IgE were tested with an allergen screening system. The polymerase chain reaction–restriction fragment length polymorphism method was used to analyze the two SNPs. Among the finally included 437 patients aged from 16 to 85 years, 68.2 % was positive for the total serum IgE, 49.2 % was positive for at least one of the assayed allergen-specific IgE, and 35.0 % was sensitive to house dust mite. In the SNPs analysis, the GG/(GA?AA) ratio and G/A ratio for the -403G[A locus in the male and/or female C45 years subgroup were significantly lower in the total serum IgE positive patients than in the negative patients (P\0.05). Weak linkage disequilibrium was found between -403A and -28C alleles in male subgroups adjusted by age. Conclusively, house dust mite was the most common allergen in ASD patients, and -403A allele of CCL5 promoter was a risk factor for IgE-mediated sensitization.

Six new dammarane-type triterpene saponins from Panax ginseng flower buds and their cytotoxicity

Ke-Ke Li,Sha-Sha Li,Fei Xu,Xiao-Jie Gong 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

Background: Panax ginseng has been used for a variety of medical purposes in eastern countries formore than two thousand years. From the extensive experiences accumulated in its long medication usehistory and the substantial strong evidence in modern research studies, we know that ginseng hasvarious pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascularsystemeprotective effects. The active chemical constituents of ginseng, ginsenosides, are rich instructural diversity and exhibit a wide range of biological activities. Methods: Ginsenoside constituents from P. ginseng flower buds were isolated and purified by variouschromatographic methods, and their structures were identified by spectroscopic analysis and comparisonwith the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromidemethod was used to test their cytotoxic effects on three human cancer cell lines. Results: Six ginsenosides, namely 6’emalonyl formyl ginsenoside F1 (1), 3beacetoxyl ginsenoside F1 (2),ginsenoside Rh24 (6), ginsenoside Rh25 (7), 7behydroxyl ginsenoside Rd (8) and ginsenoside Rh26 (10)were isolated and elucidated as new compounds, together with four known compounds (3e5 and 9). Inaddition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values,a tentative structureeactivity relationship was also discussed based on the results of our bioassay. Conclusion: The study of chemical constituents was useful for the quality control of P. ginseng flowerbuds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxicactivities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51and 20.48 mM, respectively.