scholarly journals Comprehensive analysis of ceRNA network of ERCC4 in colorectal cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12647
Author(s):  
Huixin Hu ◽  
Songyi Liu ◽  
Aining Chu ◽  
Jing Chen ◽  
Chengzhong Xing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Network ◽  
Drug Sensitivity ◽  
Hazard Ratio ◽  
High Expression ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Cerna Network ◽  
Kaplan Meier

Objective ERCC4 is one of the most significant molecules of Nucleotide Excision Repair (NER), which has been researched due to its high expression in colorectal cancer (CRC). This study aimed to find out the ceRNA (competitive endogenous RNA) network of ERCC4 in CRC. Methods and Materials Pan cancer mRNA expression of ERCC4 was evaluated using TCGA database. The protein expression of ERCC4 was evaluated based on the Human Protein Atlas (HPA). We screened DElncRNAs and DEmiRNAs in two groups of ERCC4high and ERCC4low expression in CRC. Then a lncRNA-miRNA-ERCC4 regulatory network was constructed based on DElncRNAs and DEmiRNAs using Starbase database and visualized by Cytoscape software. Kaplan-Meier analysis was performed to evaluate the prognostic value of the ceRNA network. Further, RT-PCR was performed to validate the expression of the representative molecules in the ceRNA network in CRC and normal tissues. The relationship between drug sensitivity and these molecules were also evaluated using RNAactDrug database. Results ERCC4 was overexpressed in a variety of tumors at mRNA levels, including CRC. High expression of ERCC4 was also observed on protein level in CRC. A total of 1,885 DElncRNAs and 68 DEmiRNAs were identified from CRC samples in ERCC4high and ERCC4low expression groups. Predicted by the Starbase database, we got interacting miRNAs and lncRNAs of ERCC4 from the DEmiRNAs and DElncRNAs, and a lncRNA-miRNA-ERCC4 regulatory network was constructed. Kaplan-Meier survival curves results showed that miR-200c-3p (hazard ratio [HR] = 0.62, P = 0.032), MALAT1 (HR = 1.54, P = 0.016), and AC005520.2 (hazard ratio [HR] = 1.75, P = 0.002) were significantly associated with the prognosis of CRC. After validation by RT-PCR, we found that ERCC4 and MALAT1 were up-regulated in CRC compared with normal tissues, while miR-200c-3p was down-regulated. A strong negative correlation was observed between MALAT1 and miR-200c-3p. Drug sensitivity analysis showed that ERCC4, miR-200c and MALAT1 were all associated with Cisplatin. Conclusion We constructed a ceRNA network of ERCC4 in CRC, of which the MALAT1-miR-200c-3p-ERCC4 axis may be involved in the development, prognosis and chemotherapy sensitivity of CRC. These findings might provide novel clues and insights on the molecular mechanisms of ERCC4 and NER pathway in CRC.

scholarly journals High expression of HSP90 is associated with poor prognosis in patients with colorectal cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7946 ◽  
Author(s):  
Shuming Zhang ◽  
Shichao Guo ◽  
Zhangfu Li ◽  
Dan Li ◽  
Qimin Zhan
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Proportional Hazards ◽  
Excision Repair ◽  
Critical Role ◽  
Metabolic Process ◽  
Mrna Levels ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Hsp90 Expression

Background Heat shock protein 90 (HSP90) is a highly conserved chaperone with an approximate molecular weight of 90-kDa. It plays a critical role in maintaining stability and homeostasis of oncoproteins, helping cancer cells living in the unsuitable environmental conditions. The current study aims to inquire the difference of HSP90 expression in tumor tissues and normal tissues, analyze the correlation between HSP90 expression and the prognoses of patients with colorectal cancer (CRC), and investigate its role in CRC preliminarily. Methods Online analysis of HSP90 mRNA levels in different cancers was firstly done in Gene Expression Profiling Interactive Analysis. Then HSP90 expression was determined by immunohistochemistry between 99 CRC tissues and 81 normal tissues. Chi-square test or Fisher’s exact test was used to analyze the relationship between HSP90 and histopathologic characteristics. Kaplan–Meier analysis and Cox’s proportional hazards model were also done for further analysis of the prognostic values of HSP90. Pearson’s correlation coefficients between HSP90 expression values and other mRNA expression values were calculated based on The Cancer Genome Atlas dataset and bioinformatic analysis was done about these screened genes. Results Colorectal cancer tissues showed significantly higher expression of HSP90 than normal tissues (55.6% vs. 3.7%, P < 0.0001). Kaplan–Meier curves showed high HSP90 expression was associated with poor prognosis (P = 0.039) in CRC patients, and multivariate Cox proportional hazards regression model analysis also indicated that HSP90 expression (HR = 1.930, 95% CI [1.113–3.349], P = 0.019) linked to poor prognosis. Moreover, 85 genes were correlated with HSP90, which were involved in metabolic process and enriched in pathways of Proteasome and Base excision repair. Conclusions Our results suggested that HSP90 expression is inversely associated with survival outcomes and could be an independent prognostic factor for CRC patients. It mainly involved in metabolic process and exerted binding and catalytic activities.

Prognostic value of biglycan in gastric cancer

2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Mrna Levels ◽  
Gene Signatures ◽  
Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

scholarly journals A Functional Polymorphism in the Promoter Region of Interleukin-12B Increases the Risk of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yabin Liu ◽  
Binghui Li ◽  
Lili Wang ◽  
Dexian Kong
Keyword(s):  
Colorectal Cancer ◽  
Direct Sequencing ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Normal Tissues ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Healthy Control ◽  
Polymerase Chain ◽  
Interleukin 12B

Objective. To investigate whether the polymorphisms of interleukin-12B (IL-12B) were associated with the risk of developing colorectal cancer (CRC). Patients and Methods. Genotypes of rs17860508 and rs3212227 were determined by polymerase chain reaction with a direct sequencing method in 329 CRC patients and 342 matched healthy control subjects. The expression of IL-12B mRNA was determined by RT-qPCR in 50 pairs of CRC tissues and their adjacent normal tissues. Results. Compared with TTAGAG/TTAGAG genotype of rs17860508, the GC/GC and TTAGAG/GC genotypes may significantly increase the risk of CRC (OR = 1.81, 95% CI = 1.18–2.78; OR = 1.46, 95% CI = 1.01–2.12, respectively). Furthermore, the mRNA levels of IL-12B were significantly higher in the CRC tissues from patients with the rs17860508 GC/GC genotype than those with the TTAGAG/GC (P=0.009) and TTAGAG/TTAGAG (P=0.001) genotypes. Conclusion. These data suggested that the rs17860508 GC/GC genotype might upregulate IL-12B expression at the transcriptional level and thus increase the risk of CRC.

scholarly journals Prognostic roles of microRNA 143 and microRNA 145 in colorectal cancer: A meta-analysis

2019 ◽  
Vol 34 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Chenyao Li ◽  
Guoqiang Yan ◽  
Libin Yin ◽  
Tao Liu ◽  
Chao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hazard Ratio ◽  
High Expression ◽  
Cochrane Library ◽  
Event Free Survival ◽  
Free Survival ◽  
High Event ◽  
Low Expression

Background: A systematic analysis was conducted to clarify the relationship between miR-143/145 and the prognosis of colorectal cancer. Materials and methods: We searched four databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies. Each individual hazard ratio was used to calculate the pooled hazard ratio. Results: A total of 17 articles including 5128 patients were ultimately included. The results showed that there was no significant difference between low expression and high expression of miR-143 in the overall survival of colon cancer patients. However, low expression of miR-143 was significantly associated with high event-free survival (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.40, 0.88). Low expression of miR-145 was associated with poor prognosis of patients (HR 1.92; 95% CI 1.45, 2.54); those with low expression of miR-145 were at 1.92-fold higher risk for short-term overall survival than those with high expression of miR-145. MiR-145 was an unfavorable factor for the prognosis of colorectal cancer. There were no significant differences between low expression of miR-145 and high expression of miR-143 in event-free survival. Conclusion: miR-143 and miR-145 have promising prognostic value for colorectal cancer. Low expression of miR-143 can predict high event-free survival, and low expression of miR-145 can predict poor overall survival.

Homeobox B9: A potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10531-10531
Author(s):  
Yoshinori Hoshino ◽  
Tetsu Hayashida ◽  
Akira Hirata ◽  
Koji Okabayashi ◽  
Hiroki Ochiai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Surrogate Marker ◽  
Angiogenic Factors ◽  
High Expression ◽  
Mrna Levels ◽  
Tgfβ Signaling ◽  
Bevacizumab Treatment

10531 Background: Homeobox B9 (HOXB9) is known to be overexpressed in human breast cancer and profoundly related to tumorigenicity, lung metastasis and radio-resistance. (Hayashida, PNAS 2010, and Chiba, PNAS 2011). However, little is known about the relation between the expression of HOXB9 and angiogenesis in colorectal cancer (CRC). We aimed to clarify the impact of HOXB9 in CRC and evaluate the importance for bevacizumab treatment. Methods: The expression of HOXB9 in human CRC specimens was analyzed. Then, we introduced HOXB9 construct into human CRC cell lines and examined TGFβ signaling and angiogenic factors. Xenograft model was established by these cell lines either with or without the administration of bevacizumab (5mg/kg, weekly) intraperitoneally. Finally, we examined the mRNA levels of consecutive patients who were treated by chemotherapy with bevacizumab in our institute and calculated the Kaplan- Meier curve with log-rank test. Results: 47 of 69 surgical specimens (67%) showed positive expression of HOXB9 mRNA. The high HOXB9 mRNA levels significantly correlated with poor differentiation and liver metastasis. The HOXB9-overexpressed cell lines showed significantly higher expression of TGFβ signaling target genes and angiogenic factors. HOXB9 overexpression significantly increased tumor volume and burden with higher microvessel density in vivo, even though the cell proliferation decreased in vitro. Notably, HOXB9-overexpressed tumor was dramatically shrunk by administration of bevacizumab (tumor shrinkage rate; 93% vs. 42% in HT29, 83% vs. 27% in HCT116). Patients with high expression of HOXB9 in tumor showed significantly longer progression free and overall survival periods (n=39). Conclusions: Our results demonstrated that patients with high expression of HOXB9 in tumor had better prognosis with bevacizumab treatment but worse without. In vivo and in vitro experiments revealed that HOXB9 might orchestrate angiogenesis and establish positive feedback between cancer cells and microenvironment. Bevacizumab might inhibit the feedback to reduce tumor growth dramatically. Therefore, HOXB9 may work as a potential surrogate marker of bevacizumab treatment in CRC.

scholarly journals Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Limei Liu ◽  
Jiaomin Yang ◽  
Chao Wang
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Normal Breast ◽  
Mrna Levels ◽  
Growth And Survival ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Kaplan Meier ◽  
Solute Carrier ◽  
Breast Tissues

Abstract Background: Breast cancer (BC) is the most common malignancy in females and remains a main cause of cancer-associated death worldwide. The solute carrier (SLC) groups of membrane transport proteins, which control the influx of zinc, participate in ranging of physiological processes and may provide novel therapeutic targets of cancers. However, the prognostic values of individual SLC family 39 (SLC39A) genes in patients with BC are not clarified. Materials and Methods: The mRNA expression of SLC family 39 genes in BC was evaluated by using the UALCAN database. The prognostic values of overall survival (OS) of SLC family 39 genes in patients with BC were investigated by Kaplan–Meier plotter. The survival analysis of cells was determined by Project Achilles. Results: The analytic results suggested that SLC39A1, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A9, SLC39A10, SLC39A11 and SLC39A13 were significantly up-regulated in BC tissues compared with normal breast tissues. However, SLC39A8 and SLC39A14 were expressed higher in normal tissues than in BC tissues. High expression of SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A7, SLC39A12 and SLC39A13 was significantly associated with worse OS in patients with BC. In contrast, high mRNA levels of SLC39A6 and SLC39A14 indicated favorable OS. Through subgroup analysis, all abnormal expressed SLC family members were correlated with prognoses of patients with specific BC. Moreover, SLC39A7 was associated with proliferation and cloning of BC. Conclusions: Our results suggested that SLC family 39 members were promising prognostic biomarkers of BC. The SLC39A7 played a key role in growth and survival of BC cells.

scholarly journals Bioinformatics Identification of Prognostic Factors Associated With Breast Cancer

2020 ◽  
Author(s):  
wei ying ◽  
Shipeng Zhang ◽  
Li Xiao ◽  
Jing Zou ◽  
Yingqing Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Candidate Genes ◽  
Regulatory Network ◽  
Breast Cancer Cells ◽  
Ppi Network ◽  
Rt Pcr ◽  
Positive Regulation ◽  
Normal Cells ◽  
Kaplan Meier

Abstract Background: Breast cancer (BRCA) remains one of the most common forms of cancer and is the most prominent driver of cancer-related death among women. The mechanistic basis for BRCA, however, remains incompletely understood. In particular, the relationships between driver mutations and signaling pathways in BRCA are poorly characterized, making it difficult to identify reliable clinical biomarkers that can be employed in diagnostic, therapeutic, or prognostic contexts.Methods: First, we downloaded publically available BRCA datasets (GSE45827, GSE42568, and GSE61304) from the Gene Expression Omnibus (GEO) database. We then compared gene expression profiles between tumor and control tissues in these datasets using Venn diagrams and the GEO2R analytical tool. We further explore the functional relevance of BRCA-associated differentially expressed genes (DEGs) via functional and pathway enrichment analyses using the DAVID tool, and we then constructed a protein-protein interaction network incorporating DEGs of interest using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Modules within this PPI network were then identified using Cytoscape, leading to the identification of key candidate genes. The prognostic relevance of these candidate genes was then established through Kaplan-Meier survival analyses and further Gene Expression Profiling Interactive Analysis (GEPIA) validation. Then, key gene-target miRNA regulatory network and transcription factor-key gene regulatory relationships were established using the online miRWalk2.0, TargetScan7.2, miRDB and TRRUST tools. Moreover, four representative key molecules (AURKA, RRM2, BIRC5, and E2F1) were optionally chosen for verification by using quantitative real-time polymerase chain reaction (RT-PCR) and western blot.Results: We identified 85 BRCA-related DEGs across these three datasets. The 31 upregulated DEGs were found to be enriched for pathways and functions including mitotic nuclear division, cell division, G2/M transition of mitotic cell cycle, collagen catabolic process, endodermal cell differentiation, oocyte meiosis, ECM-receptor interactions, and p53 signaling pathway. The 54 downregulated DEGs were, in contrast, enriched in pathways and functions such as lipid metabolic processes, lipid transport, regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ions, positive regulation of cell proliferation, positive regulation of cell-matrix adhesion, tyrosine metabolism, cytochrome P450 drug metabolism, protein digestion and absorption, and PPAR signaling. We were further able to select 16 upregulated candidate genes of interest from our PPI network, and in subsequent Kaplan-Meier analyses we were able to determine that elevated expression of 14 of these genes was associated with a poorer BRCA patient prognosis. We then employed GEPIA to validate these 14 gene candidates, confirming them to all be expressed at elevated levels in BRCA relative to normal tissue controls. In addition, a regulatory network consisting of 9 genes, 10 miRNAs and 3 TFs was constructed, enabling the identification of potential biomarkers of BRCA, including AURKA, RRM2, BIRC5, and E2F1. RT-PCR results suggested that significantly elevated AURKA, RRM2 and BIRC5 mRNAs expressed in the breast cancer cells than in the normal cells. Western blot results shown that E2F1 protein was highly expressed in breast cancer cells compared to normal cells. In conclusion, these candidate molecules may offer insight regarding the underlying pathogenesis of BRCA and highlight a number of potential therapeutic avenues for the treatment of breast cancer patients.

scholarly journals Identification of Novel Survival Related lncRNA-miRNA-mRNA Competing Endogenous RNA Network Associated with Immune Infiltration in Colorectal Cancer

2020 ◽  
Author(s):  
Jianxin Li ◽  
Ting Han ◽  
Xin Wang ◽  
Yinchun Wang ◽  
Qingqiang Yang
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Network ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Competing Endogenous Rna ◽  
Expression Levels ◽  
Go Annotation ◽  
Immune Infiltration ◽  
Cerna Network

Abstract Background: Increasing studies have reported that long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of carcinogenesis. However, the underlying regulatory mechanisms of lncRNA related competing endogenous RNA (ceRNA) network in colorectal cancer (CRC) are not fully understood.Methods: Dysregulated microRNAs (miRNAs) in CRC samples were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. After that, the key miRNAs were filtered out through a comprehensive assessment of their expression levels and prognostic values. Subsequently, the targeted downstream mRNAs and upstream lncRNAs of the key miRNAs were predicted by using multiple bioinformatic databases. A ceRNA network was constructed by using Cytoscape, and the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on this network using the DAVID database. Ultimately, expression levels and prognostic values of the lncRNAs and mRNAs were evaluated, and a survival related ceRNA network was constructed and visualized by using Cytoscape. In addition, the Gene Set Enrichment Analysis (GSEA) software package was employed to identify the pathways in which this survival related ceRNA network was enriched. Furthermore, correlations of ceRNA network with immune infiltration level were estimated by the Tumor Immune Estimation Resource (TIMER) databases.Results: In total, 28 dysregulated miRNAs were obtained, and two of them were identified as key miRNAs based on expression levels and prognostic values analyses. Subsequently, a total of three upstream lncRNAs and 309 downstream mRNAs were predicted by using bioinformatic tools, and two key lncRNAs and eight key mRNAs were identified by expression and survival analysis. A ceRNA regulatory network associated with the prognosis of CRC patients was constructed. Furthermore, GSEA analysis indicated the possible association of key mRNAs with CRC onset and progression. Importantly, immune infiltration analysis revealed that the ceRNA network was remarkably associated with infiltration abundance of multiple immune cells and expression levels of immune checkpoints.Conclusions: We constructed a survival related ceRNA regulatory network in human CRC, NEAT1 and XIST are potential prognostic factors that affect CRC onset and progression by targeting miR-195-5p.

scholarly journals Functional analysis of lncRNAs based on competitive endogenous RNA in tongue squamous cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6991 ◽  
Author(s):  
Yidan Song ◽  
Yihua Pan ◽  
Jun Liu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Regulatory Network ◽  
Curve Analysis ◽  
Tongue Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
High Expression ◽  
Kaplan Meier ◽  
Competitive Endogenous Rna

BackroundTongue squamous cell carcinoma (TSCC) is the most common malignant tumor in the oral cavity. An increasing number of studies have suggested that long noncoding RNA (lncRNA) plays an important role in the biological process of disease and is closely related to the occurrence and development of disease, including TSCC. Although many lncRNAs have been discovered, there remains a lack of research on the function and mechanism of lncRNAs. To better understand the clinical role and biological function of lncRNAs in TSCC, we conducted this study.MethodsIn this study, 162 tongue samples, including 147 TSCC samples and 15 normal control samples, were investigated and downloaded from The Cancer Genome Atlas (TCGA). We constructed a competitive endogenous RNA (ceRNA) regulatory network. Then, we investigated two lncRNAs as key lncRNAs using Kaplan–Meier curve analysis and constructed a key lncRNA-miRNA-mRNA subnetwork. Furthermore, gene set enrichment analysis (GSEA) was carried out on mRNAs in the subnetwork after multivariate survival analysis of the Cox proportional hazards regression model.ResultsThe ceRNA regulatory network consists of six differentially expressed miRNAs (DEmiRNAs), 29 differentially expressed lncRNAs (DElncRNAs) and six differentially expressed mRNAs (DEmRNAs). Kaplan-Meier curve analysis of lncRNAs in the TSCC ceRNA regulatory network showed that only two lncRNAs, including LINC00261 and PART1, are correlated with the total survival time of TSCC patients. After we constructed the key lncRNA-miRNA -RNA sub network, the GSEA results showed that key lncRNA are mainly related to cytokines and the immune system. High expression levels of LINC00261 indicate a poor prognosis, while a high expression level of PART1 indicates a better prognosis.

scholarly journals ANRIL promotes chemoresistance via disturbing expression of ABCC1 by regulating the expression of Let-7a in colorectal cancer

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Zhen Zhang ◽  
Lifeng Feng ◽  
Pengfei Liu ◽  
Wei Duan
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Clinical Prognosis ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Oncogenic Gene ◽  
Poor Clinical Prognosis

Increasing evidence indicates that long non-coding RNAs (lncRNAs) antisense non-coding RNA in the INK4 locus (ANRIL) has been involved in various diseases and promotes tumorigenesis and cancer progression as an oncogenic gene. However, the effect of ANRIL on chemoresistance remains still unknown in colorectal cancer (CRC). Here, we investigated ANRIL expression in 63 cases of colorectal cancer specimens and matched normal tissues. Results revealed that ANRIL was up-regulated in tumor tissues samples from patients with CRC and CRC cell lines. Increased ANRIL expression in CRC was associated with poor clinical prognosis. Kaplan–Meier analysis showed that ANRIL was associated with overall survival of patients with colorectal cancer, and patients with high ANRIL expression tended to have unfavorable outcome. In vitro experiments revealed that ANRIL knockdown significantly inhibited CRC cell proliferation, improved the sensitivity of chemotherapy and promoted apoptosis. Further functional assays indicated that ANRIL overexpression significantly promoted cell chemoresistance by regulating ATP-binding cassette subfamily C member 1 through binding Let-7a. Taken together, our study demonstrates that ANRIL could act as a functional oncogene in CRC, as well as a potential therapeutic target to inhibit CRC chemoresistance.

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