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Datta A, R HC, Udhaya Kumar S, Vasudevan K, Thirumal Kumar D, Zayed H, George Priya Doss C. Molecular characterization of circadian gene expression and its correlation with survival percentage in colorectal cancer patients. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 137:161-180. [PMID: 37709374 DOI: 10.1016/bs.apcsb.2023.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Colorectal cancer (CRC) is a form of cancer characterized by many symptoms and readily metastasizes to different organs in the body. Circadian rhythm is one of the many processes that is observed to be dysregulated in CRC-affected patients. In this study, we aim to identify the dysregulated physiological processes in CRC-affected patients and correlate the expression profiles of the circadian clock genes with CRC-patients' survival rates. We performed an extensive microarray gene expression pipeline, whereby 471 differentially expressed genes (DEGs) were identified, following which, we streamlined our search to 43 circadian clock affecting DEGs. The Circadian Gene Database was accessed to retrieve the circadian rhythm-specific genes. The DEGs were then subjected to multi-level functional annotation, i.e., preliminary analysis using ClueGO/CluePedia and pathway enrichment using DAVID. The findings of our study were interesting, wherein we observed that the survival percentage of CRC-affected patients dropped significantly around the 100th-month mark. Furthermore, we identified hormonal activity, xenobiotic metabolism, and PI3K-Akt signaling pathway to be frequently dysregulated cellular functions. Additionally, we detected that the ZFYVE family of genes and the two genes, namely MYC and CDK4 were the significant DEGs that are linked to the pathogenesis and progression of CRC. This study sheds light on the importance of bioinformatics to simplify our understanding of the interactions of different genes that control different phenotypes.
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Affiliation(s)
- Ankur Datta
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Hephzibah Cathryn R
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - S Udhaya Kumar
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Karthick Vasudevan
- Department of Biotechnology, School of Applied Sciences, REVA University, Bengaluru, Karnataka, India
| | - D Thirumal Kumar
- Faculty of Allied Health Sciences, Meenakshi Academy of Higher Education and Research (MAHER), Chennai, Tamil Nadu, India
| | - Hatem Zayed
- Department of Biomedical Sciences, College of Health and Sciences, Qatar University, QU Health, Doha, Qatar
| | - C George Priya Doss
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
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Yang Z, Lu S, Wang Y, Tang H, Wang B, Sun X, Qu J, Rao B. A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer. Int J Gen Med 2022; 15:555-565. [PMID: 35046713 PMCID: PMC8763259 DOI: 10.2147/ijgm.s349624] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022] Open
Abstract
Objective This study aims at exploring the relationship between necroptosis-related miRNAs and colon cancer prognosis. Methods We downloaded the miRNA sequencing data from the TCGA, and eight differentially expressed necroptosis-related miRNAs were screened. Then, we used Cox regression analysis to establish a prediction model of necroptosis-related miRNA. Finally, the prognosis related miRNAs were used to predict the target genes, and functional analysis was used to explore the potential mechanism of these target genes. Results The miRNA-seq data of 444 COAD cases were downloaded from TCGA. We identified 8 differentially expressed miRNAs (has-miR-16-5p, has-miR-141-3p, has-miR-148a-3p, has-miR-425-5p, has-miR-7-5p, has-miR-223-3p, has-miR-200a-5p, and has-miR-500a-3p), then Cox analysis was performed for determining eight-miRNA signature prognostic biomarkers with obviously different OS. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for predicting 1-, 3-, and 5-year survival were 0.663, 0.653 and 0.639, respectively. The multivariate analysis also implied that the risk score was an independent prognostic factor considering other confounding factors (HR = 1.847, 95% CI = 1.197–2.848, P = 0.006). According to the Kaplan–Meier analysis, the expression of hsa-miR-500a-3p (P = 0.003), hsa-miR-16-5p (P = 0.004) and hsa-miR-148a-3p (P = 0.035) significantly affected OS outcomes. We predicted the target genes of these three miRNAs and then screened 10 hub genes (CCND1, SMAD3, SMAD2, CDK1, TGFB2, CDC25A, CHEK1, VEGFA, CCNE1, WEE1). In addition, CHEK1 was associated with the survival prognosis. Conclusion Our study demonstrated that necroptosis is closely associated with colon cancer, and the model of eight necroptosis-related miRNAs are potentially useful prognostic biomarkers and therapeutic targets for colon cancer.
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Affiliation(s)
- Zhenpeng Yang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
| | - Shuai Lu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
| | - Yuying Wang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
| | - Huazhen Tang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
| | - Bing Wang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
| | - Xibo Sun
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China
| | - Jinxiu Qu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
| | - Benqiang Rao
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China
- Correspondence: Benqiang Rao Tel +86 13521237767 Email
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First person – Swati Priya. J Cell Sci 2021. [DOI: 10.1242/jcs.259172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Swati Priya is first author on ‘CDX2 inducible microRNAs sustain colon cancer by targeting multiple DNA damage response pathways factors’, published in JCS. Swati is a Postdoctoral fellow in the lab of Dr Sagar Sengupta at National Institute of Immunology, New Delhi, India, working on identifying the role of microRNAs (miRs) in different types of cancer, such as colon cancer, rectal cancer and B cell lymphoma, and the regulation of miRs by Bloom helicase.
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