Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs

Sun, Xia; Hu, Yingying; Liang, Zhen; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guiqian; Xue, Xiangyang; Guo, Aijiang; Shen, Xian

doi:10.1371/journal.pone.0164590

Cited by 14 publications

(13 citation statements)

References 36 publications

(34 reference statements)

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“…TCGA and GEO are international public repositories that contain a large number of genomic datasets, and several genes that have diagnostic value in colorectal cancer have been found using these datasets [ [27] , [28] , [29] , [30] ]. Using bioinformatics analysis, we found that SETD7 , but not FGA and MUC5AC , is expressed at significantly higher levels in CRC than in normal colorectal mucosa tissue.…”

Section: Discussionmentioning

confidence: 99%

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

et al. 2018

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BackgroundThere is an urgent need for the identification of new, clinically useful biomarkers of CRC to enhance diagnostic and prognostic capabilities.MethodsWe performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. We examined SETD7 expression in serum and tissue samples by ELISA and immunohistochemistry respectively and explored the biological function of SETD7 in vitro.Findings85 differentially expressed peptides were identified. Five peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased after surgery. The sensitivity and specificity of SETD7 were 92.17% and 81.08%, with a high diagnostic value (AUC = 0.9477). In addition, SETD7 expression was significantly correlated with tumor stage and microsatellite instability. Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest and increased apoptosis.InterpretationOur data indicate that SETD7 could serve as a potential diagnostic and prognostic biomarker for CRC.

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Section: Discussionmentioning

confidence: 99%

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

et al. 2018

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“…Many studies have investigated the lncRNAs involved in the development, diagnosis, and prognosis of colon cancer. For instance, Sun et al (2016) found a lncRNA (AK098081) that can serve as an independent risk factor for colon cancer by analysis of GEO datasets (150 cases). Moreover, Li et al (2017) identified eight novel lncRNAs associated with the prognosis of colon cancer.…”

Section: Discussionmentioning

confidence: 99%

A 7-lncRNA signature associated with the prognosis of colon adenocarcinoma

Duanmu

et al. 2020

PeerJ

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Background Colon adenocarcinoma (COAD) is the most common colon cancer exhibiting high mortality. Due to their association with cancer progression, long noncoding RNAs (lncRNAs) are now being used as prognostic biomarkers. In the present study, we used relevant clinical information and expression profiles of lncRNAs originating from The Cancer Genome Atlas database, aiming to construct a prognostic lncRNA signature to estimate the prognosis of patients. Methods The samples were randomly spilt into training and validation cohorts. In the training cohort, prognosis-related lncRNAs were selected from differentially expressed lncRNAs using the univariate Cox analysis. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were employed for identifying prognostic lncRNAs. The prognostic signature was constructed by these lncRNAs. Results The prognostic model was able to calculate each COAD patient’s risk score and split the patients into groups of low and high risks. Compared to the low-risk group, the high-risk group had significant poor prognosis. Next, the prognostic signature was validated in the validation, as well as all cohorts. The receiver operating characteristic (ROC) curve and c-index were determined in all cohorts. Moreover, these prognostic lncRNA signatures were combined with clinicopathological risk factors to construct a nomogram for predicting the prognosis of COAD in the clinic. Finally, seven lncRNAs (CTC-273B12.10, AC009404.2, AC073283.7, RP11-167H9.4, AC007879.7, RP4-816N1.7, and RP11-400N13.2) were identified and validated by different cohorts. The Kyoto Encyclopedia of Genes and Genomes analysis of the mRNAs co-expressed with the seven prognostic lncRNAs suggested four significantly upregulated pathways, which were AGE-RAGE, focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways. Conclusion Thus, our study verified that the seven lncRNAs mentioned can be used as biomarkers to predict the prognosis of COAD patients and design personalized treatments.

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“…The rising incidence and high metastasis of CRC has become an urgent problem in diagnosis and treatment (Sun et al, ), but unfortunately, lack of the information about the molecular mechanism in CRC, has brought a considerable burden on CRC treatment (Zhang, Yang, & Chen, ). Thus, more investigation of biological function or molecular mechanism should be carried out.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding MAGI2‐AS3 promotes colorectal cancer progression through regulating miR‐3163/TMEM106B axis

Ren

Zheng-jun

et al. 2019

Journal Cellular Physiology

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Colorectal cancer (CRC), is mostly derived from normal colon epithelial cells, and has been reported to be one of most common gastrointestinal malignancies globally. An increasing number of researchers have claimed that long noncoding RNAs (lncRNAs) exert significant functions in tumor progression. Nevertheless, the function of MAGI2-AS3 remains uncertain in CRC. The expression of MAGI2-AS3, miR-3163, and transmembrane protein 106B (TMEM106B) messenger RNA was examined by quantitative real-time polymerase chain reaction. Cell apoptosis was measured by caspase-3 activity test. Cell proliferation was tested by cell-counting kit 8 and 5-ethynyl-2′-deoxyuridine assays. Cell migration was detected by transwell assay. Western blot analysis examined the protein expression of TMEM106B. The expression of Ki-67 was evaluated by immunohistochemistry assay. The binding capacity between miR-3163 and MAGI2-AS3 (or TMEM106B) was studied by radioimmunoprecipitation and luciferase reporter assays. The expression of MAGI2-AS3 and TMEM106B was conspicuously upregulated whereas miR-3163 presented lower expression in CRC cells. MAGI2-AS3 deficiency facilitated cell apoptosis but hampered cell proliferation and migration. MAGI2-AS3 combined with miR-3163 and negatively regulated miR-3163 expression. In addition, the administration of sh-MAGI2-AS3 or miR-3163 mimics suppressed CRC cell growth in vivo. Subsequently, miR-3163 targeted TMEM106B and the transfection of sh-MAGI2-AS3 or miR-3163 mimics downregulated TMEM106B expression. Rescue assays verified that TMEM106B overexpression recovered the effects of MAGI2-AS3 inhibition on cell apoptosis, proliferation, and migration in CRC. MAGI2-AS3 drives CRC progression through regulating miR-3163/TMEM106B axis. This supplies innovative insights on the investigation of molecular mechanism in CRC progression. K E Y W O R D S CRC, MAGI2-AS3, miR-3163, TMEM106B

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Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs

Cited by 14 publications

References 36 publications

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

A 7-lncRNA signature associated with the prognosis of colon adenocarcinoma

Long noncoding MAGI2‐AS3 promotes colorectal cancer progression through regulating miR‐3163/TMEM106B axis

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