Identification of Molecular Targets for Predicting Colon Adenocarcinoma

Wang, Yansheng; Zhang, Jun; Li, Li; Xu, Xin; Zhang, Yong; Teng, Zhaowei; Wu, Feihu

doi:10.12659/msm.895881

Cited by 14 publications

(8 citation statements)

References 31 publications

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“…Colon adenocarcinoma (COAD) is one of the malignant cancers and ranks the third leading cause of cancer‐related mortality across the globe . Although interventions have improved the survival time for the early detected patients, prognosis is still poor for the advanced stage colon cancer patients even if they receive standard management (surgery, chemotherapy, as well as radiotherapy) .…”

Section: Introductionmentioning

confidence: 99%

miR‐4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma

et al. 2019

J Biochem & Molecular Tox

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To date, microRNA‐4709 (miR‐4709) has not been studied in colon adenocarcinoma (COAD) on the basis of experiments. In our study, we aimed to investigate the biological roles and clinical significance of miR‐4709 in COAD. The expression difference between miR‐4709 and NR3C2 was measured based on The Cancer Genome Atlas database and cells. Kaplan‐Meier and logrank tests were applied to determine the overall survival (OS) differences according to the miR‐4709 and NR3C2 expression levels. To measure whether the miR‐4709 level was associated with COAD cell growth, migration, and invasion, we respectively conducted 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, wound healing, and transwell assays. A luciferase reporter assay was applied to confirm the relationship between miR‐4709 and its predicted target. High expression of miR‐4709 was found in COAD tissues and cells. The OS rate in the miR‐4709 low expression group was significantly higher than that in the miR‐4709 high expression group. Univariate and multivariate analyses exhibited that miR‐4709 expression was an independent adverse prognostic factor. Exogenous miR‐4709 overexpression promoted proliferation, migration, and invasion of LOVO and SW480 cells. Bioinformatics analysis and luciferase assay demonstrated that miR‐4709 directly binds to the 3′‐untranslated region of NR3C2. NR3C2 was lowly expressed in COAD and high expression of NR3C2 had a better prognosis compared with that in the low expression of NR3C2. Correlation analysis showed that there is a close association between the level of expression of NR3C2 and miR‐4709. Accordingly, miR‐4709 may function as an oncogene in COAD and provide a preclinical proof for candidate management to target new miR‐4709‐NR3C2 signaling for COAD therapy.

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Section: Introductionmentioning

confidence: 99%

miR‐4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma

et al. 2019

J Biochem & Molecular Tox

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“…Cytoscape and STRING (https://stringdb.org/) were also utilized to visualize the prognostic DELs and their corresponding co-expressed genes as a network [34][35][36][37][38].…”

Section: Functional Analysis Of the Selected Prognostic Delsmentioning

confidence: 99%

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

Huang²,

et al. 2018

Cell Physiol Biochem

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Background/Aims: Current practical advances in high-throughput data technologies including RNA-sequencing have led to the identification of long non-coding RNAs (lncRNAs) for potential clinical application against bladder urothelial cancer (BLCA). However, most previous studies focused on the clinical value of individual lncRNAs, which has limited the potential for future clinical application. Methods: In this study, RNA-sequencing data of lncRNAs was downloaded from The Cancer Genome Atlas database. Risk score was constructed based on survival-associated lncRNAs identified using differential expression analysis as well as univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic and Kaplan-Meier curve analyses were employed to evaluate the clinical and prognostic value of risk scores. Bioinformatics analyses were used to investigate the potential mechanisms of newly identified lncRNAs. Results: Among 2,127 differentially expressed lncRNAs (DELs), four new lncRNAs (AC145124.1, AC010168.2, MIR200CHG, and AC098613.1) showed valuable prognostic effects in BLCA patients. More importantly, the four-DEL-based risk score had the potential to become an independent marker for the survival status prediction of BLCA patients. Distinct co-expressed genes and signaling pathways were identified when BLCA was categorized into low- and high-risk groups. Furthermore, a protein-coding gene, HIST4H4 was found only 68 bp from the AC010168.2 DEL. HIST4H4 expression level was evidently up-regulated and positively correlated with AC010168.2 in BLCA patients. Conclusion: This in silico investigation pioneers the future investigation of the utility of prognostic lncRNAs for BLCA.

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“…As a class of endogenous, small non-coding RNAs, microRNAs (miR-NAs) have been indicated to be involved in COAD as well. 1 MiRNAs not only can act as oncogenes and tumor suppressors directly 4,5 but also play a role in COAD by regulating the expression of their targeting genes. 6,7 Hence, identifying the key miRNAs in early-stage COAD is also crucial.…”

Section: Introductionmentioning

confidence: 99%

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

Liu

et al. 2017

Tumour Biol.

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Colon adenocarcinoma is the third leading cause of cancer-related deaths across the world, developing novel and non-invasive diagnostic and prognostic biomarkers for the early-stage colon adenocarcinoma at molecular level is essential. In our study, RNA-sequencing was performed to identify the differentially expressed genes and miRNAs (DEmiRNAs) in early-stage colon adenocarcinoma compared to tissues of precancerous lesions, colonic intraepithelial neoplasia. The DEmiRNA-target interaction network was constructed and functional annotation of targets of DEmiRNAs was performed. The Cancer Genome Atlas was used to verify the expression of selected differentially expressed genes. The receiver operating characteristic analyses of selected differentially expressed genes was performed. In total, 865 differentially expressed genes, 26 DEmiRNAs, and 329 DEmiRNA-target pairs were obtained. Based on the early-stage colon adenocarcinoma network, miR-548c-5p, miR-548i, and miR-548am-5p were the top three DEmiRNAs that covered most differentially expressed genes. NTRK2, DTNA, and BTG2 were the top three differentially expressed genes regulated by most DEmiRNAs. Cancer and colorectal cancer pathways were two significantly enriched pathways in early-stage colon adenocarcinoma. The common differentially expressed genes in both the pathways were AXIN2, Smad2, Smad4, PIK3R1, and BCL2. The expression levels of eight differentially expressed genes (NTRK2, DTNA, BTG2, COL11A1, Smad2, Smad4, PIK3R1, and BCL2) in The Cancer Genome Atlas database were compatible with our RNA-sequencing. All these eight differentially expressed genes and AXIN2 had the potential diagnosis value for Colon adenocarcinoma. In conclusion, a total of ten differentially expressed genes (NTRK2, DTNA, BTG2, COLCA1, COL11A1, AXIN2, Smad2, Smad4, PIK3R1, and BCL2) and four DEmiRNAs (miR-548c-5p, miR-548i, mir-424-5p, and miR-548am-5p) may be involved in the pathogenesis of early-stage colon adenocarcinoma which may make a contribution for developing new diagnostic and therapeutic strategies for early-stage colon adenocarcinoma.

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Identification of Molecular Targets for Predicting Colon Adenocarcinoma

Cited by 14 publications

References 31 publications

miR‐4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma

miR‐4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

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