Identification of potential hub genes via bioinformatics analysis combined with experimental verification in colorectal cancer

Zhou, Hongrui; Yang, Zhe; Yue, Jiaxin; Chen, Yang; Chen, Tianqiao; Mu, Teng; Liu, Huan; Bi, Xiuli

doi:10.1002/mc.23165

Cited by 14 publications

(8 citation statements)

References 40 publications

(61 reference statements)

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“…Colon cancer is a very common cancer worldwide with high morbidity and mortality. Several kinetochore proteins have been identified as a novel regulator of carcinogenesis in colorectal cancer (Dang et al 2020;Bai et al Zhou et al 2020;Zhang et al 2021). In the present study, KNTC1, a key kinetochore component, was shown to be overexpressed in colon cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

KNTC1 knockdown suppresses cell proliferation of colon cancer

et al. 2021

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Kinetochore-associated protein 1 (KNTC1) is a kind of kinetochore components that ensure the proper functioning of the spindle-assembly checkpoint. To date, the functional information of KNTC1 in colon cancer remains unknown. This study was aimed to investigate the role of KNTC1 in colon cancer. We found KNTC1 was significantly upregulated in the colon cancer compared to the normal tissues. ROC curve showed the area under the curve value of KNTC1 for the prediction of colon cancer was 0.93. Kaplan-Meier revealed highly expressed KNTC1 was associated with poor prognosis. KNTC1 was widely expressed in different colon cancer cell lines. Compared with the control lentiviral infected cells, KNTC1-shRNA cells exhibited significant reduction in cell growth rates and increase in the proportion of cells in the S phase, while decrease in the G1 and G2/M phase. Furthermore, knockdown of KNTC1 dramatically increased apoptosis in the colon cancer cells. Gene set enrichment analysis (GSEA) in gene ontology (GO) showed that KNTC1 is closely associated with cell mitosis-related components, such as nuclear chromatin, centrosome, and spindle. Moreover, upregulated KNTC1 is significantly enriched in the biological process of DNA repair, mRNA processing, microtubule cytoskeleton organization and the molecular function of helicase activity, protein heterodimerization activity and catalytic activity acting on DNA in molecular function. Our data reveal the important roles of KNTC1 in driving tumor progression in colon cancers. KeywordsKNTC1 • Colon cancer • Cell growth • GSEA * Yang Zhimin

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Section: Discussionmentioning

confidence: 99%

KNTC1 knockdown suppresses cell proliferation of colon cancer

et al. 2021

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“…All the images and annotations in the database are available for download. The analysis of the data for the immunohistochemical staining of STAT3 protein expression refers to a previous study [33]. Statistical analysis was performed using SPSS version 21.0, and the p-value was determined using the Mann-Whitney U-test.…”

Section: The Human Protein Altas Databasementioning

confidence: 99%

Significance of STAT3 in Immune Infiltration and Drug Response in Cancer

et al. 2020

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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and regulates tumorigenesis. However, the functions of STAT3 in immune and drug response in cancer remain elusive. Hence, we aim to reveal the impact of STAT3 in immune infiltration and drug response comprehensively by bioinformatics analysis. The expression of STAT3 and its relationship with tumor stage were explored by Tumor Immune Estimation Resource (TIMER), Human Protein Altas (HPA), and UALCAN databases. The correlations between STAT3 and immune infiltration, gene markers of immune cells were analyzed by TIMER. Moreover, the association between STAT3 and drug response was evaluated by the Cancer Cell Line Encyclopedia (CCLE) and Cancer Therapeutics Response Portal (CTRP). The results suggested that the mRNA transcriptional level of STAT3 was lower in tumors than normal tissues and mostly unrelated to tumor stage. Besides, the protein expression of STAT3 decreased in colorectal and renal cancer compared with normal tissues. Importantly, STAT3 was correlated with immune infiltration and particularly regulated tumor-associated macrophage (TAM), M2 macrophage, T-helper 1 (Th1), follicular helper T (Treg), and exhausted T-cells. Remarkably, STAT3 was closely correlated with the response to specified inhibitors and natural compounds in cancer. Furthermore, the association between STAT3 and drug response was highly cell line type dependent. Significantly, the study provides thorough insight that STAT3 is associated with immunosuppression, as well as drug response in clinical treatment.

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“…DSN1 is a component of the MIS12 kinetochore complex localized at the kinetochores in the mitotic cells and involved in the cell cycle. Based on bioinformatic analysis and experimental verification, Zhou et al (2020), revealed that silencing of DSN1 could have a therapeutic effect and significantly reduced the migration and proliferation of colorectal cancer (CRC).…”

Section: Discussionmentioning

confidence: 99%

Identification of miR‐3182 and miR‐3143 target genes involved in the cell cycle as a novel approach in TNBC treatment: A systems biology approach

et al. 2022

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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, lacking therapeutic targets. miRNAs play crucial roles in TNBC through regulating various mechanisms, including cellular growth and proliferation. This study aims to identify critical target genes of two novel miRNAs (miR-3143 and miR-3182) involved in the cell cycle of TNBC as possible therapeutic targets and investigates their regulatory and therapeutic roles through a systems biology approach and in vitro experiment. Datasets related to the TNBC cell line (MDA-MB-231) were screened and retrieved, and Gene regulatory networks were constructed. Significant regulatory motifs were detected and analyzed using the FANMOD and Cytoscape analyzer, and the clusters and seeds were identified using the MCODE. Functional enrichment analysis was also performed using DAVID and STRING. The most critical genes were determined using the analysis of GRN motifs and PPI clusters. The essential genes involved in the cell cycle were selected and verified using the bc-GenExMiner v4.7. We overexpressed miR-3143 and miR-3182 in the MDA-MB-231 cell line using human umbilical cord mesenchymal stem cell (HUCMSC)-miRNA loaded exosomes, and the expression of the critical target genes was investigated using RT-qPCR. We identified eight critical genes as potential therapeutic targets. Their expression decreased by overexpression of miR-3143 and miR-3182 in RT-qPCR.The identified critical genes have probably significant roles in the pathogenesis of TNBC through the cell cycle. We suggest that the overexpression of miR-3143

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Identification of potential hub genes via bioinformatics analysis combined with experimental verification in colorectal cancer

Cited by 14 publications

References 40 publications

KNTC1 knockdown suppresses cell proliferation of colon cancer

KNTC1 knockdown suppresses cell proliferation of colon cancer

Significance of STAT3 in Immune Infiltration and Drug Response in Cancer

Identification of miR‐3182 and miR‐3143 target genes involved in the cell cycle as a novel approach in TNBC treatment: A systems biology approach

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