bluuebunny/crossref_metadata_2025_split huggingface dataset:
NR2F1‐AS1 regulated miR‐423‐5p/SOX12 to promote proliferation and invasion of papillary thyroid carcinoma
Authors: Yang Chuanjia , Liu Zhen , Chang Xiaoying , Xu Weixue , Gong Jian , Chai Fang , Cui Dongxu 
Published: November 2019

AbstractPapillary thyroid carcinoma (PTC) is an aggressive histological subtype of thyroid carcinoma (THCA), whose occurrence rate is high. The participation of long noncoding RNAs in the pathologies of cancers has attracted significant attention during the past decades. The purpose of the current study is to investigate the role of NR2F1 antisense RNA 1 (NR2F1‐AS1) in PTC. The expression of NR2F1 in THCA samples was analyzed by bioinformatics tool gene expression profiling interactive analysis. Levels of NR2F1‐AS1, microRNA‐423‐5p (miR‐423‐5p), and SRY‐box 12 (SOX12) were evaluated by a quantitative reverse transcription‐polymerase chain reaction and Western blot. The impact of NR2F1‐AS1 on PTC cell proliferation and invasion was assessed by Cell Counting Kit‐8, EdU, and Transwell invasion assays. The interactions among NR2F1‐AS1, miR‐423‐5p, and SOX12 were determined by RNA immunoprecipitation and luciferase reporter assays. Consequently, we found that NR2F1‐AS1 and SOX12 levels were elevated in PTC, whereas miR‐423‐5p was downregulated in PTC cells. Functionally, NR2F1‐AS1 silence led to reduced proliferation and invasion of PTC cells. Mechanistically, NR2F1‐AS1 interacted with miR‐423‐5p to induce SOX12 expression in PTC cells. In conclusion, the present study firstly stated that NR2F1‐AS1 regulated miR‐423‐5p/SOX12 to promote proliferation and invasion of PTC, indicating NR2F1‐AS1 as a potential novel target for the molecular‐targeted therapy of PTC.
FOXO3 gene polymorphisms influence the risk of acute lymphoblastic leukemia in Chinese children
Authors: Yang Xu , Wu Xuedong , Fang Na , Liu Xiaoping , Liu Xiaodan , Yang Lihua , Huang Ke , Luo Ailing , Cai Mansi , Wu Fan , Jiang Hua , Xu Ling 
Published: November 2019

AbstractAcute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children and single‐nucleotide polymorphisms (SNPs) in certain genes influence risk of ALL. Although FOXO3 had been demonstrated to be involved leukemia, the role of FOXO3 polymorphisms was still not clear. In the present study, we explored the association of FOXO3 SNPs with ALL risk in Chinese children. We genotyped four polymorphisms (rs17069665 A>G, rs4945816 T>C, rs4946936 C>T, and rs9400241 A>C) of FOXO3 in 425 ALL cases and 1339 health controls. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Further analyses were performed to explore associations of rs17069665 and rs9400241 with ALL susceptibility in terms of age, gender, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. We found rs17069665 related to the increased ALL risk (OR = 1.76; 95% CI = 1.02‐3.04), rs9400241 related to decreased ALL risk (OR = 0.80; 95% CI = 0.64‐0.99). The effects of rs17069665 on ALL risk were more predominant in males and children < 10 years, and patients with lower rates of platelet or neutrophil. As for rs9400241, the effects were more predominant in children < 10 years, and in patients with pre B ALL, positive MRD, anemia, or hepatomegaly. In conclusion, FOXO3 gene polymorphisms influence the risk of ALL in children and might be a potential biomarker for ALL susceptibility.
lncRNA GAS5‐promoted apoptosis in triple‐negative breast cancer by targeting miR‐378a‐5p/SUFU signaling
Authors: Zheng Shipeng , Li Mengquan , Miao Keke , Xu Han 
Published: November 2019

AbstractPurposeLong‐chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth‐stasis specific transcript 5 (GAS5) on triple‐negative breast cancer (TNBC).MethodsQuantitative real‐time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a‐5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo.ResultsIn this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum‐free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR‐378 could directly bind to each other. Moreover, the miR‐378a‐5p target of SUFU could promote lncRNA GAS5‐induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA‐231R could enhance the sensitivity of TNBC to PTX.ConclusionThe above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR‐378a‐5p/SUFU signaling.
Molecular chaperone HspB2 inhibited pancreatic cancer cell proliferation via activating p53 downstream gene RPRM, BAI1, and TSAP6
Authors: Yu Ze , Wang Hao , Fang Yilin , Lu Liangliang , Li Minghao , Yan Bingru , Nie Yuzhe , Teng Chunbo 
Published: November 2019

AbstractHeat shock proteins (HSPs) were known as the molecular chaperones, which play a pivotal role in the protein quality control system, ensuring correct folding of proteins, and facilitating the correct refolding of damaged proteins via the transient interaction with their substrate proteins. They also practice in the regulation of cell cycles and are involved in apoptosis. We found that HspB2 was almost completely silent in pancreatic cancer and few studies investigated the role of HspB2 in cancer cells, particularly in pancreatic cancer. Here, we reported that HspB2 effectively inhibited cell proliferation in Panc‐1 cells. Specifically, we demonstrated that HspB2 could combine mut‐p53 and change the DNA binding site of mutant p53, subsequently upregulated the expression of RPRM, BAI‐1, and TSAP6 which were the downstream genes of wt‐p53, participate in mediating downstream responses to p53, including inhibiting cell proliferation and angiogenesis. The main aim of this study is to investigate the relationship between HspB2 and p53, and provide a novel treatment strategy for pancreatic cancer.
DNA methylation and gene expression profiles characterize epigenetic regulation of lncRNAs in colon adenocarcinoma
Authors: Li Zhijin , Tan Hua , Yu Hai , Deng Zhong , Zhou Xiaobo , Wang Maode 
Published: November 2019

AbstractThe long noncoding RNAs (lncRNAs) are associated with tumorigenesis and progression of cancer. While DNA methylation is a common epigenetic regulator of gene expression, the methylation of lncRNAs was rarely studied. To address this gap, we integrated DNA methylation and RNA‐seq data to characterize the landscape of lncRNA methylation in colon adenocarcinoma (COAD). We collected and analyzed the lncRNA expression and methylation data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia to identify the epigenetically regulated lncRNAs. We further investigated the biological and clinical relevance of the identified lncRNAs via bioinformatics analysis. We identified 20 epigenetically upregulated lncRNAs in COAD, including several well‐studied lncRNAs whose methylation regulation were poorly investigated, such as PVT1 and UCA1. We also revealed several novel tumor‐associated lncRNAs in COAD, including GATA2‐As1 and CYTOR. Next, we explored their biology function using gene set enrichment analysis and competitive endogenous RNA analysis. We characterized the methylation landscape of lncRNA in COAD and identified 20 epigenetically upregulated lncRNAs. Our findings will shed new light on the epigenetic regulation of lncRNA expression by DNA methylation.
FASTKD2 promotes cancer cell progression through upregulating Myc expression in pancreatic ductal adenocarcinoma
Authors: Fang Rui , Zhang Bin , Lu Xiaoming , Jin Xin , Liu Tao 
Published: November 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers of the digestive system. Despite the development of novel therapeutic methods, including chemotherapy, radiotherapy, and molecular targeted therapy, the incidence rate of PDAC is almost equal to the mortality rate with 5‐year overall survival rate less than 5%. Kras mutation is found in 95% of patient with PDAC specimens, but targeting Kras mutation do not benefit patients with pancreatic cancer in preclinical trials. c‐Myc is one of the main effector molecules of the Kras signaling pathway. In this study, we found that dysregulation of FAST kinase–domain‐containing protein 2 (FASTKD2) resulted in the poor prognosis of patients with PDAC. Then, we showed that FASTKD2 promoted pancreatic cancer cell proliferation and invasion. Importantly, we demonstrated that c‐Myc was transcriptionally increased by FASTKD2/BRD4 axis and responsible for FASTKD2‐mediated tumor growth and invasion in pancreatic cancer cells. Collectively, this study uncovered that FASTKD2 promoted cancer cell progression through upregulating Myc expression in pancreatic cancer. FASTKD2 might be a potential target for pancreatic cancer therapy.
LINC00958 facilitates cervical cancer cell proliferation and metastasis by sponging miR‐625‐5p to upregulate LRRC8E expression
Authors: Wang Lifeng , Zhong Yanbo , Yang Baohua , Zhu Yunheng , Zhu Xiuxiang , Xia Ziyin , Xu Jun , Xu Ling 
Published: November 2019

AbstractAccepted as a malignant tumor worldwide, cervical cancer (CC) has attracted much attention for its high incidence and mortality rates. Previous studies have elucidated the critical regulatory function that long noncoding RNAs (lncRNAs) exert on the tumorigenesis and progression of diverse tumors. Although multiple investigations have depicted that LINC00958 has a great impact on the complex biological process of many cancers, knowledge concerning the regulatory role of LINC00958 in CC remains limited and needs to be further explored. In our study, LINC00958 expression was evidently overexpressed in CC tissues and cells. Besides this, LINC00958 negatively regulated miR‐625‐5p expression and was verified to bind with miR‐625‐5p in CC. Subsequently, it was testified by a series of experiments that LINC00958 promotes CC cell proliferation and metastasis by sponging miR‐625‐5p. Furthermore, the leucine‐rich repeat containing the eight family member E (LRRC8E) could bind with miR‐625‐5p, and its expression was negatively modulated by miR‐625‐5p, whereas positively regulated by LINC00958 in CC. Final rescue assays verified the effects of LINC0095/LRRC8E interaction and miR‐625‐5p/LRRC8E interaction on CC cell proliferation and metastasis. Collectively, LINC00958 facilitates CC cell proliferation and metastasis via the miR‐625‐5p/LRRC8E axis.
BTN3A2 serves as a prognostic marker and favors immune infiltration in triple‐negative breast cancer
Authors: Cai Peian , Lu Zhenhui , Wu Jianjun , Qin Xiong , Wang Zetao , Zhang Zhi , Zheng Li , Zhao Jinmin 
Published: November 2019

AbstractImmune infiltration is reported to be highly associated with tumor progress. Since butyrophilin subfamily 3 member A2 (BTN3A2) serves as a crucial mediator in immune activation, we aimed to investigate the correlation of BTN3A2 in immune infiltration and tumor prognosis via extensive‐cancer analysis. The levels of BTN3A2 expression in extensive cancers were analyzed with Oncomine and TIMER databases. Univariate cox and multivariate cox regression analyses were conducted to assess the associations of BTN3A2 to prognosis of various cancers. The correlations of BTN3A2 with immune infiltration were assessed by TIMER database. It suggested that BTN3A2 was a potential prognosis signature for breast cancer (BRCA) and ovarian cancer (OV). However, immune infiltrations were highly correlated with BTN3A2 in triple‐negative breast cancer (TNBC), compared with OV and other subtypes of BRCA. Multivariate cox regression analysis revealed that BTN3A2 was an independently prognostic signature of TNBC, as well as weighted correlation network analysis suggested BTN3A2 was only correlated with TNBC, rather than other subtypes of BRCA. Immune cell subtypes correlation analysis showed that BTN3A2 was highly correlated with general T, CD8+ T, T helper type 1, exhausted T cells, and dendritic cells in TNBC. And the coexpression geneset of BTN3A2 was mainly involved in T‐cell receptor interaction and the nuclear factor‐κB (NF‐κB) signaling pathway. Collectively, BTN3A2 that was positively associated with better prognosis could be served as a special diagnostic and independently prognostic marker for TNBC by regulating the T‐cell receptor interaction and NF‐κB signaling pathways.
Targeting BAX ubiquitin‐binding sites reveals that BAX activation is essential for its ubiquitin‐dependent degradation
Authors: Peng Rui , Zhu Jialin , Deng Shujin , Shi Hui , Xu Shutao , Wu Hongjuan , Zou Fangdong 
Published: November 2019

AbstractBAX is an important proapoptotic protein of the BCL‐2 family, and its stability is essential for the regulation of the mitochondrial apoptotic pathway. A previous study revealed that BAX could undergo degradation through the ubiquitin‐proteasome pathway. In this study, we identified two lysine sites, K21 and K123, that were critical ubiquitin‐binding sites in BAX. Mutation of these two sites prolonged the half‐life of BAX and also affected its proapoptotic ability. Intriguingly, we found that ABT‐737, a BCL‐2 inhibitor, significantly enhanced TRAIL‐induced BAX degradation in HCT116 cells and increased TRAIL‐induced apoptosis in the HCT116 only with the BAX K21R/K123R mutant, not other BAX mutants. In addition, overexpression of PARKIN, an E3 ubiquitin ligase targeting BAX, dramatically decreased BAX protein level when only treated with ABT‐737 in HCT116 cells. Therefore, we speculated that BAX activation is essential for its ubiquitin‐dependent degradation.
KRAS mutation and abnormal expression of Cripto‐1 as two potential candidate biomarkers for detection of colorectal cancer development
Authors: Igder Somayeh , Mohammadiasl Javad , Azadpour Shima , Mansouri Esrafil , Ashktorab Hassan , Mokarram Pooneh 
Published: November 2019

AbstractColorectal cancer (CRC), regardless of standard procedures of treatment and screening, is still considered one of the deadliest cancers in the Western world, and in economically developed Asian countries, especially Iran. The current study was undertaken to investigate whether changes in the level of Cripto‐1 (CR‐1) expression and KRAS mutations have a cumulative effect on the onset and progression of CRC. Fifty colorectal tissue samples, including 35 colorectal carcinomas with matching adjacent mucosa, and 15 colorectal adenomas, were chosen for analysis. Twenty‐five CRC biopsies and 15 adenoma were analyzed for KRAS mutations by DNA sequencing (Sanger sequencing), and all 50 patients (35 CRCs and 15 adenomas) were evaluated by immunohistochemistry for the CR‐1 protein expression. The inducible somatic KRAS mutation (G12D) was observed in nine (36%) of CRC patients, and in two (13.3%) of adenoma patients. The CR‐1 expression level in both adenomas (P < .05) and carcinomas (P < .001), were significantly different, compared with the matching adjacent mucosa. The intensity of CR‐1 staining in adenomas was less than the intensity of staining, detected in the CRCs (P < .001). The G12D KRAS mutation and CR‐1 abnormalities are significantly associated as two signature biomarkers with potential clinical characteristics for the detection of CRC development.
Nano CuO–Ag‐catalyzed synthesis of some novel pyrano[2,3‐d] pyrimidine derivatives and evaluation of their bioactivity
Authors: Poola Sreelakshmi , Shaik Mahammad S. , Sudileti Murali , Yakkate Subbarao , Nalluri Vedasree , Chippada Apparao , Cirandur Suresh R. 
Published: November 2019

AbstractA simple, highly efficient, and green method is developed for the synthesis of pyrano[2,3‐d] pyrimidine derivatives via Knoevenagel and Michael addition in the presence of nano CuO–Ag as a catalyst. The structures of synthesized target compounds 5a–l were confirmed by spectral and elemental analysis and were screened for their antioxidant activity by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), H2O2, and NO methods. Their antibacterial activity against Gram‐negative bacteria Pseudomonas aeruginosa and Escherichia coli, against Gram‐positive bacteria such as Bacillus subtilis and Staphylococcus aureus, and antifungal activity against Candida albicans and Candida glabrata was also evaluated. The compounds showed higher bacterial activity than the standard used. Compounds 5b, 5d, 5g, 5h, and 5i exhibited higher free radical scavenging activity than the standard butylated hydroxy toluene (BHT). Compounds 5b, 5d, and 5h showed higher activity on Gram‐positive bacteria, and compounds 5b, 5d, 5h, and 5i showed higher activity on Gram‐negative bacteria than that of standard tetracycline. Compounds 5b, 5j, and 5l showed much higher antifungal activity against Candida globrata and C. albicans than that of standard Griseofulvin.
Evaluation of the clinical performance of the HISCL‐5000 analyzer in the detection of Krebs von den Lungen‐6 antigen and its diagnostic value in interstitial lung disease
Authors: Wang Jingxian , Huang Zhifeng , Xue Mingshan , Huang Huimin , Zheng Xiaomao , Zhong Nanshan , Sun Baoqing 
Published: November 2019

AbstractBackgroundThe sputum saccharide chain antigen (Krebs von den Lungen‐6 [KL‐6]) is a serum biomarker of lung injury. We aimed to evaluate the clinical performance of the automated immunoassay analyzer HISCL‐5000 in detecting KL‐6 by comparing it with LUMIPULSE G1200 and determine the diagnostic value of KL‐6 in interstitial lung disease (ILD).MethodsA total of 145 serum samples from patients were tested using the two automated immunoassay analyzers in parallel.ResultsWith a cutoff level of 500 U/mL, comparing the two systems, the agreement, sensitivity, specificity, and kappa value were 99.20%, 100%, 98.63%, and 0.984 (95% CI, 0.952‐1.000), respectively. Spearman's correlation and ICC showed that there was a strong correlation between serum KL‐6 levels measured by the two systems (rS = .991 [95% CI, 0.981‐0.995], ICC = 0.984 [95% CI, 0.978‐0.989], P < .01). The clinical diagnosis agreement rate in both systems was >80%. The kappa value was 0.707 (95% CI, 0.582‐0.832; SYSTEM B) and 0.707 (95% CI, 0.588‐0.826; SYSTEM A). The KL‐6 level in the ILD group (1339.5, 662.5‐2363) was significantly higher than that in the non‐ILD groups (252, 158.5‐353; Mann‐Whitney U = 381.5, P < .01), and the KL‐6 level (1558, 726‐2772.5) in the ILD group detected by SYSTEM A was significantly higher than that in the lung cancer group (339, 207‐424), other respiratory disease group (249, 194‐366), and control group (198, 131.5‐297; Kruskal‐Wallis H = 63.19, P < .01).ConclusionsHISCL‐5000 showed well‐concordant results with those of HISCL‐5000 in the KL‐6 tests. In patients with ILD, KL‐6 showed a good diagnostic performance.
Clinical significance of serum bilirubin in primary Sjögren syndrome patients
Authors: Zhang Zunni , Su Qisheng , Zhang Liqian , Yang Zheng , Qiu Yuling , Mo Wuning 
Published: November 2019

AbstractObjectiveThe purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS).Patients and methodsA total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed.ResultsSerum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = −.406, P < .001; r = −.206, P = .026; r = −.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR.ConclusionsThis study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow‐up visits of the patients with pSS.
Posttranscriptional regulation of MMP‐9 by HuR contributes to IL‐1β‐induced pterygium fibroblast migration and invasion
Authors: Cui Yu‐Hong , Feng Qing‐Yang , Liu Qun , Li Hong‐Yang , Song Xi‐Ling , Hu Zi‐Xuan , Xu Zhi‐Yi , Li Jia‐Hui , Li Mei‐Jun , Zheng Wen‐Lin , Li Zhi‐Jie , Pan Hong‐Wei 
Published: November 2019

AbstractInflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase‐9 (MMP‐9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The influence of interleukin‐1β (IL‐1β) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP‐9 production was determined with qRT‐PCR and gelatin zymography. The interaction between HuR and MMP‐9 was investigated with RNP immunoprecipitation (IP) followed by RT‐PCR and messenger RNA (mRNA) stability analysis. HuR and MMP‐9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL‐1β could increase the expression and nucleus–cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL‐1β on PTF migration and MMP‐9 production. HuR bound to MMP‐9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP‐9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL‐1β on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.