scholarly journals ASXL2 promotes colorectal cancer tumorigenesis by inducing cell proliferation

2020 ◽  
Author(s):  
Ran Cui ◽  
Ludi Yang ◽  
Yiwei Wang ◽  
Ming Zhong ◽  
Minhao Yu ◽  
...  

Abstract Background: Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of trithorax and polycomb gene, which have been proved to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors have been extensively studied in recent years. However the relationship between ASXL2 and the prognosis of CRC is still unclear.Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on proliferation of CRC cells were determined by CCK8 assay.Results: This study demonstrated that ASXL2 was significantly more expressed in CRC specimens relative to the normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stages. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed ASXL2 expression could be considered as an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells.Conclusion: These results showed that ASXL2 could induce cell proliferation which is associated with poor prognosis of CRC patients and might be a new therapeutic target for CRC.

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


2021 ◽  
Author(s):  
Gang Liu ◽  
Xiaowang WU ◽  
Jian Chen

Abstract Background Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with high mortality rate. Because of malignancy and easily metastasis feather, and limited treatments, the prognosis of CC remains poor. Glycolysis is a metabolic process of glucose in anoxic environments which is an important way to provide energy for tumor. The role of glycolysis in CC largely remains unknown and is necessary to be explored. Method In our study, we analyzed glycolysis related genes expression in CC, patients gene expression and corresponding clinical data were downloaded from GEO dataset, glycolysis related genes sets were collected from Msigdb. Through COX regression analysis, prognosis model based on glycolysis-related genes was established. The efficacy of gene model was tested by Survival analysis, ROC analysis and PCA analysis. Furthermore, the relationship between risk scores and clinical characteristic was researched. Results Our findings identified 13 glycolysis related genes (NUP107, SEC13, ALDH7A1, ALG1, CHPF, FAM162A, FBP2, GALK1, IDH1, TGFA, VLDLR, XYLT2 and OGDHL) consisted prognostic prediction model with relative high accuracy. The relationship between prediction model and clinical feathers were specifically studied, results showed age > 65years, TNM III-IV, T3-4, N1-3, M1 and high-risk score were independent prognostic risk factors with poorer prognosis. Finally, model genes were significantly expressed and EMT were activated in CC patients. Conclusion This study provided a new aspect to advance our understanding in the potential mechanism of glycolysis in CC.


2017 ◽  
Vol 32 (1) ◽  
pp. 108-112 ◽  
Author(s):  
Da-Kai Zhou ◽  
Xi-Wang Yang ◽  
Huining Li ◽  
Yongbo Yang ◽  
Zhen-Jun Zhu ◽  
...  

Background Long noncoding RNAs (IncRNAs) play essential roles in tumor progression. Aberrant colorectal cancer-associated IncRNA (CCAL) has been found in colorectal cancer. However, the function of IncRNA CCAL in osteosarcoma (OS) remains unclear. Methods Quantitative real-time PCR (qRT-PCR) was performed to measure CCAL expression in OS tissues and adjacent nontumor tissues. The correlation betweent CCAL expression and clinicopathological features and prognosis was also analyzed. In addition, the function of CCAL was further evaluated by cell proliferation, migration and invasion assays. Results We showed that CCAL was significantly up-regulated in OS tissues compared with adjacent nontumor tissues. Increased expression of CCAL was correlated with advanced TNM stage and metastasis. Kaplan-Meier analysis demonstrated that patients with high CCAL expression had lower overall survival than those with low CCAL expression. Multivariate Cox regression analysis indicated that CCAL expression might be an independent prognostic factor for OS patients. In addition, functional assays showed that decreased CCAL expression could inhibit OS cell proliferation, migration and invasion ability. Conclusions Our findings suggested that CCAL plays critical roles in OS progression and could act as a therapeutic target in the treatment of OS.


2018 ◽  
Vol 12 ◽  
pp. 117955491877506 ◽  
Author(s):  
Maher Jedi ◽  
Graeme P Young ◽  
Susanne K Pedersen ◽  
Erin L Symonds

The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively ( P < .001). The IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.


Author(s):  
Xiaojian Zhu ◽  
Fanqin Bu ◽  
Ting Tan ◽  
Qilin Luo ◽  
Jinfeng Zhu ◽  
...  

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo. Results We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
He Wang ◽  
Huiwen Wang ◽  
Wenyu Cui ◽  
Qiao Zhang ◽  
Jing Li ◽  
...  

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Yang ◽  
Qi Zhang ◽  
Guo-Tian Ruan ◽  
Meng Tang ◽  
Xi Zhang ◽  
...  

BackgroundColorectal cancer (CRC) is one of the most common malignancies throughout the world, with high rates of morbidity and mortality. Previous studies reported that serum creatinine (Scr) concentrations were associated with overall survival (OS) in cancer patients, but little is known about the association between Scr and OS in patients with CRC. This study investigated the relationship between Scr concentrations and OS in patients with CRC and examined possible effect modifiers.MethodsA retrospective cohort, including 1,733 patients with CRC, was established from a multi-center clinical study. Patients were divided into low (&lt;71 μmol/L in men or &lt;59 μmol/L in women), normal (71-104 μmol/L in men or 59-85 μmol/L in women) and high (&gt;104 μmol/L in men or &gt;85 μmol/L in women) Scr groups. Cox regression analysis was used to examine association between Scr concentrations and OS. Stratified (subgroup) analyses were used to examine men and women separately. Interaction tests were used to evaluate associations between each variable and OS, as well as possible interactions of these variables with Scr levels. Cross-classified analyses were used only in men.ResultsPatients with low [hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.19-1.72; P &lt; 0.001] or high (HR = 1.89, 95% CI = 1.36-2.63; P &lt; 0.001) Scr level had a significantly lower OS than patients with normal Scr levels. Significant interactions with Scr concentrations were observed for body mass index (P for interaction = 0.019) in men.ConclusionLow or high Scr concentration is associated with significantly lower OS in patients with CRC. Future study is warranted to investigate the underlying mechanism.


2020 ◽  
Author(s):  
xiaojian zhu ◽  
Fanqin Bu ◽  
Ting Tan ◽  
Qilin Luo ◽  
Jingfeng Zhu ◽  
...  

Abstract Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods: An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivio . Results: We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo . Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo . Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions: Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.


2019 ◽  
pp. 108-111
Author(s):  
Z. M. Galeeva ◽  
R. G. Toukhbatullina ◽  
A. I. Gaisina

The role of duodenogastric reflux (DGR) in malignant degeneration of the gastric mucosa. It was demonstrated by immunohistochemistry using monoclonal antibodies to p53, PCNA, CD10, MUC2, MUC5AC, MUC6, CD31 and the polymerase chain reaction to detect CDX1, CDX2, FXR genes. The main carcinogenic components of bile are lysolecithin and conjugated bile acids. Biliary reflux increases the risk of malignant tumors in combination with Helicobacter pylori. DGR is one of the etiological factors for gastric cancer, so it determines the necessity for detailed diagnosis in clinical practice.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Peng ◽  
Si Lei ◽  
Quan Zhang ◽  
Yanjun Zhong ◽  
Shangjie Wu

BackgroundCigarette smoking has been proven to be a risk factor in the development of many diseases. However, it remains controversial with respect to the relationship of smoking with COVID-19. The purpose of this study was to explore the role of smoking in COVID-19.MethodsA total of 622 patients with COVID-19 in China were enrolled in the study. Corresponding clinical and laboratory data were collected and analyzed. Meanwhile, Kaplan-Meier curve and Cox regression analysis were employed to analyze the association of smoking with survival in patients with COVID-19.ResultsSmoking was statistically significant comparing non-survivors and survivors of patients with COVID-19 (P = 0.007). Males had higher proportion of smoking than females (91.9% vs. 8.1%, P &lt; 0.001). Compared with the non-smoker, there was significant statistical difference in the incidence of cerebrovascular disease in smoking patients with COVID-19 (9.7% vs. 3.4%, P = 0.017). White blood cell count (6.3 vs. 5.4; P = 0.037), hemoglobin level (139.0 vs. 127.0; P &lt; 0.001), and creatinine level (77.3 vs. 61.0; P &lt; 0.001) were significantly increased in COVID-19 patients who smoked. Moreover, smoking patients showed a worse survival compared with non-smoking patients (Log Rank P = 0.045). After adjustment for age, gender and underlying diseases, patients with smoking still had higher risk of mortality than that of non-smoking patients (hazard ratio[HR] 1.897, 95% confidence interval [CI]1.058–3.402, P = 0.032).ConclusionSmoking was thought to be a risk factor in predicting the prognosis of COVID-19 and smoking patients might have a higher risk of mortality than that of the non-smoking patients.


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