Expression profiling based on graph-clustering approach to determine colon cancer pathway

Zhu, Xiao-qu; Hu, Meilan; Zhang, Na; Tao, Yu; Wu, Chun‐Ming; Lin, Shang-zhu; He, Fu-le

doi:10.4103/0973-1482.119351

Cited by 4 publications

(2 citation statements)

References 20 publications

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“…AKAP12 , which belongs to the family of kinase scaffolding proteins, designated as a tumor suppressor gene which was detected in colorectal carcinoma tissues 24. In our previous work, we found that re-expression of AKAP12 inhibits progression and metastatic potential in CRC cell lines 13.…”

Section: Discussionmentioning

confidence: 98%

AKAP12 Endogenous Transcripts Suppress The Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Directly Targeting oncomiR-183-5p

Hu¹,

Wu²,

Li³

et al. 2019

OTT

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PurposeRestoring lost function to suppressor gene products has captured the interest of the research community in the field of gene therapy. AKAP12, also known as Gravin/AKAP250, is a tumor suppressor gene, and its deregulation may be responsible for cancer progression. The aim of this study was to investigate whether AKAP12 mRNA has an anti-cancer function by regulating onco-miRNA expression in colorectal cancer (CRC) cells.MethodsmiRNAs targeting AKAP12 were predicted by bioinformatics analysis and further confirmed by dual-luciferase reporter assays and RT-qPCR. The altered expression of microRNA was validated in early-stage CRC tumor tissues by miRseq. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay. Cell invasion and migration were detected by transwell and wound healing assays, respectively. In vivo experiments were conducted to confirm the in vitro findings.ResultsAmong all miRNAs, reversed correlation between AKAP12 expression and miRNA-183-5p expression was most significant. Luciferase assays revealed that AKAP12 directly targeted miR-183-5p. The miRseq data showed that miR-183 was also dysregulated at the early stage of tumor development and upregulated in late sub-stage II CRC patients (P<0.01). Mechanistic analysis both in vitro and in vivo demonstrated that anti-miR-183-5p depressed cell proliferation, migration, and invasion in CRC cells while miR-183-5p overexpression resulted in opposite effects.ConclusionOur findings suggested that oncomiR-183-5p promoted the proliferation, migration, and invasion of CRC cells. AKAP12 miRNA-binding elements (MREs) suppressed miRNA-183-5p activities. Any change in expression of AKAP12 thus affected miRNA-183-5p. This may be another anti-tumor mechanism in addition to protein-mediation that regulates tumor suppressor genes.

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Section: Discussionmentioning

confidence: 98%

AKAP12 Endogenous Transcripts Suppress The Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Directly Targeting oncomiR-183-5p

Hu¹,

Wu²,

Li³

et al. 2019

OTT

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“…This analysis indicated that six pathways were significantly enriched in the high-risk group, including axon guidance, GnRH signaling, MAPK signaling, melanogenesis, vascular smooth muscle contraction, and VEGF signaling pathways. All six of these pathways have been associated with poor prognosis for CRC ( Je et al, 2013 ; Zhu et al, 2013 ; Hohla et al, 2014 ; Sun et al, 2018 ; Lu et al, 2020 ; Zhao et al, 2020a ), which may provide insight into the molecular mechanisms underlying poor prognosis in the high-risk group.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer

Xie

Yin

et al. 2021

Front. Genet.

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BackgroundImmune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC).MethodsGene expression profiles and clinical data for stage II CRC patients were collected from the Cancer Genome Atlas and Gene Expression Omnibus database. Univariate, multivariate Cox regression, and least absolute shrinkage and selection operator regression were used to develop the IRG signature, namely IRGCRCII. A nomogram was constructed, and the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method was used to estimate immune cell infiltration. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in 30 pairs of primary stage II CRC and matched normal tissues.ResultsA total of 466 patients with stage II CRC were included, and 274 differentially expressed IRGs were identified. Six differentially expressed IRGs were detected and used to construct the IRGCRCII signature, which could significantly stratify patients into high-risk and low-risk groups in terms of disease-free survival in three cohorts: training, test, and external validation (GSE39582). Receiver operating characteristics analysis revealed that the area under the curves of the IRGCRCII signature were significantly greater than those of the OncotypeDX colon signature at 1 (0.759 vs. 0.623), 3 (0.875 vs. 0.629), and 5 years (0.906 vs. 0.698) disease-free survival, respectively. The nomogram performed well in the concordance index (0.779) and calibration curves. The high-risk group had a significantly higher percentage of infiltrated immune cells (e.g., M2 macrophages, plasma cells, resting mast cells) than the low-risk group. Finally, the results of qRT-PCR and immunohistochemistry experiments performed on 30 pairs of clinical specimens were consistent with bioinformatics analysis.ConclusionThis study developed and validated a novel immune prognostic signature based on six differentially expressed IRGs for predicting disease-free survival and immune status in patients with stage II CRC, which may reflect immune dysregulation in the tumor immune microenvironment.

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Combining Structured Node Content and Topology Information for Networked Graph Clustering

Guo

Zhu

et al. 2017

ACM Trans. Knowl. Discov. Data

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Graphs are popularly used to represent objects with shared dependency relationships. To date, all existing graph clustering algorithms consider each node as a single attribute or a set of independent attributes, without realizing that content inside each node may also have complex structures. In this article, we formulate a new networked graph clustering task where a network contains a set of inter-connected (or networked) super-nodes, each of which is a single-attribute graph. The new super-node representation is applicable to many real-world applications, such as a citation network where each node denotes a paper whose content can be described as a graph, and citation relationships between papers form a networked graph (i.e., a super-graph). Networked graph clustering aims to find similar node groups, each of which contains nodes with similar content and structure information. The main challenge is to properly calculate the similarity between super-nodes for clustering. To solve the problem, we propose to characterize node similarity by integrating structure and content information of each super-node. To measure node content similarity, we use cosine distance by considering overlapped attributes between two super-nodes. To measure structure similarity, we propose an Attributed Random Walk Kernel (ARWK) to calculate the similarity between super-nodes. Detailed node content analysis is also included to build relationships between super-nodes with shared internal structure information, so the structure similarity can be calculated in a precise way. By integrating the structure similarity and content similarity as one matrix, the spectral clustering is used to achieve networked graph clustering. Our method enjoys sound theoretical properties, including bounded similarities and better structure similarity assessment than traditional graph clustering methods. Experiments on real-world applications demonstrate that our method significantly outperforms baseline approaches.

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Expression profiling based on graph-clustering approach to determine colon cancer pathway

Abstract: The results indicated calcium signaling pathway and vascular smooth muscle contraction pathway were the two significant pathways, giving hope to provide insights into the development of novel therapeutic targets and pathways.

Cited by 4 publications

References 20 publications

<p><em>AKAP12</em> Endogenous Transcripts Suppress The Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Directly Targeting oncomiR-183-5p</p>

<p><em>AKAP12</em> Endogenous Transcripts Suppress The Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Directly Targeting oncomiR-183-5p</p>

Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer

Combining Structured Node Content and Topology Information for Networked Graph Clustering

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