The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer
Abstract Circular RNAs (circRNA) are known to function as competing endogenous RNA (ceRNA) in various cancers by regulating microRNAs (miRNA). However, in colorectal cancer (CRC), the precise pathological role of circ000240/miRNA/mRNA remains indeterminate. The expression level of hsa_circ_000240 wa...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46620-z |
| _version_ | 1797630271449726976 |
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| author | Ghanbar Mahmoodi Chalbatani Elahe Gharagouzloo Mohammad Amin Malekraeisi Paniz Azizi Amirabbas Ebrahimi Michael R. Hamblin Habibollah Mahmoodzadeh Eyad Elkord Seyed Rohollah Miri Mohammad Hossein Sanati Bahman Panahi |
| author_facet | Ghanbar Mahmoodi Chalbatani Elahe Gharagouzloo Mohammad Amin Malekraeisi Paniz Azizi Amirabbas Ebrahimi Michael R. Hamblin Habibollah Mahmoodzadeh Eyad Elkord Seyed Rohollah Miri Mohammad Hossein Sanati Bahman Panahi |
| author_sort | Ghanbar Mahmoodi Chalbatani |
| collection | DOAJ |
| description | Abstract Circular RNAs (circRNA) are known to function as competing endogenous RNA (ceRNA) in various cancers by regulating microRNAs (miRNA). However, in colorectal cancer (CRC), the precise pathological role of circ000240/miRNA/mRNA remains indeterminate. The expression level of hsa_circ_000240 was evaluated using qRT-PCR in matching pairs of CRC tumor and adjacent normal tissue samples in our laboratory. Then, to determine whether hsa_circ_000240 acted as a ceRNA in CRC, the linked miRNAs and gene targets were retrieved. Topological analysis of candidate genes using a network approach identified the most critical hub genes and subnetworks related to CRC disease. Microarray and bulk RNA sequencing analyses were utilized to comprehensively evaluate the expression levels of both miRNA and mRNA in CRC. Single-cell RNA-seq analysis was also used to evaluate the significant overall survival (OS) genes at the cellular level. ATAC-seq data provided insights into candidate genes' accessible chromatin regions. The research uncovered a considerable upregulation of hsa_circ_000240 in CRC tissues. Three miRNAs interacted with the target circRNA. One thousand six hundred eighty intersected genes regulated by three miRNAs were further identified, and the relevant functionality of identified neighbor genes highlighted their relevance to cancer. The topological analysis of the constructed network has identified 33 hub genes with notably high expression in CRC. Among these genes, eight, including CHEK1, CDC6, FANCI, GINS2, MAD2L1, ORC1, RACGAP1, and SMC4, have demonstrated a significant impact on overall survival. The utilization of single-cell RNA sequencing unequivocally corroborated the augmented expression levels of CDC6 and ORC1 in individuals with CRC, alongside their noteworthy connection with the infiltration of immune cells. ATAC-seq analyses revealed altered accessibility regions in Chr2, 4, and 12 for CDC6 and ORC1 high-expression. Correlation analysis of CDC6 and ORC1 further highlighted the association of candidate gene expression with exhaustion markers such as CTLA4, CD247, TIGIT, and CD244. The candidate genes exhibit a positive correlation with chromatin remodeling and histone acetylation. These epigenetic modifications play a significant role in influencing the cancer progression following expression of CDC6 and ORC1 in CRC. Additionally, results showed that the methylation rate of the promoter region of CDC6 was elevated in CRC disease, confirming the functional importance of CDC6 and their interaction with hsa_circ_000240 and associated ceRNA in CRC. In conclusion, this study highlights hsa_circ_000240's role as a ceRNA in CRC. It opens new avenues for further dissection of CDC6, ORC1, and underlying novel epigenetics and immunotherapy targets for CRC therapy. |
| first_indexed | 2024-03-11T11:05:56Z |
| format | Article |
| id | doaj.art-d69b7a220ba94c949f686c47cf52b3ab |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:05:56Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d69b7a220ba94c949f686c47cf52b3ab2023-11-12T12:15:42ZengNature PortfolioScientific Reports2045-23222023-11-0113112710.1038/s41598-023-46620-zThe integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancerGhanbar Mahmoodi Chalbatani0Elahe Gharagouzloo1Mohammad Amin Malekraeisi2Paniz Azizi3Amirabbas Ebrahimi4Michael R. Hamblin5Habibollah Mahmoodzadeh6Eyad Elkord7Seyed Rohollah Miri8Mohammad Hossein Sanati9Bahman Panahi10Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical ScienceCancer Research Center, Cancer Institute of Iran, Tehran University of Medical ScienceStudent Research Committee, School of Medicine, Iran University of Medical SciencesPsychological and Brain Science Departments, Program in Neuroscience, Indiana UniversityCancer Research Center, Cancer Institute of Iran, Tehran University of Medical ScienceWellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical SchoolCancer Research Center, Cancer Institute of Iran, Tehran University of Medical ScienceDepartment of Applied Biology, College of Science, University of SharjahCancer Research Center, Cancer Institute of Iran, Tehran University of Medical ScienceDivision of Cellular and Molecular Biology, Department of Biology, Nour Danesh Institute of Higher EducationDepartment of Genomics, Branch for Northwest and West Region, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO)Abstract Circular RNAs (circRNA) are known to function as competing endogenous RNA (ceRNA) in various cancers by regulating microRNAs (miRNA). However, in colorectal cancer (CRC), the precise pathological role of circ000240/miRNA/mRNA remains indeterminate. The expression level of hsa_circ_000240 was evaluated using qRT-PCR in matching pairs of CRC tumor and adjacent normal tissue samples in our laboratory. Then, to determine whether hsa_circ_000240 acted as a ceRNA in CRC, the linked miRNAs and gene targets were retrieved. Topological analysis of candidate genes using a network approach identified the most critical hub genes and subnetworks related to CRC disease. Microarray and bulk RNA sequencing analyses were utilized to comprehensively evaluate the expression levels of both miRNA and mRNA in CRC. Single-cell RNA-seq analysis was also used to evaluate the significant overall survival (OS) genes at the cellular level. ATAC-seq data provided insights into candidate genes' accessible chromatin regions. The research uncovered a considerable upregulation of hsa_circ_000240 in CRC tissues. Three miRNAs interacted with the target circRNA. One thousand six hundred eighty intersected genes regulated by three miRNAs were further identified, and the relevant functionality of identified neighbor genes highlighted their relevance to cancer. The topological analysis of the constructed network has identified 33 hub genes with notably high expression in CRC. Among these genes, eight, including CHEK1, CDC6, FANCI, GINS2, MAD2L1, ORC1, RACGAP1, and SMC4, have demonstrated a significant impact on overall survival. The utilization of single-cell RNA sequencing unequivocally corroborated the augmented expression levels of CDC6 and ORC1 in individuals with CRC, alongside their noteworthy connection with the infiltration of immune cells. ATAC-seq analyses revealed altered accessibility regions in Chr2, 4, and 12 for CDC6 and ORC1 high-expression. Correlation analysis of CDC6 and ORC1 further highlighted the association of candidate gene expression with exhaustion markers such as CTLA4, CD247, TIGIT, and CD244. The candidate genes exhibit a positive correlation with chromatin remodeling and histone acetylation. These epigenetic modifications play a significant role in influencing the cancer progression following expression of CDC6 and ORC1 in CRC. Additionally, results showed that the methylation rate of the promoter region of CDC6 was elevated in CRC disease, confirming the functional importance of CDC6 and their interaction with hsa_circ_000240 and associated ceRNA in CRC. In conclusion, this study highlights hsa_circ_000240's role as a ceRNA in CRC. It opens new avenues for further dissection of CDC6, ORC1, and underlying novel epigenetics and immunotherapy targets for CRC therapy.https://doi.org/10.1038/s41598-023-46620-z |
| spellingShingle | Ghanbar Mahmoodi Chalbatani Elahe Gharagouzloo Mohammad Amin Malekraeisi Paniz Azizi Amirabbas Ebrahimi Michael R. Hamblin Habibollah Mahmoodzadeh Eyad Elkord Seyed Rohollah Miri Mohammad Hossein Sanati Bahman Panahi The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer Scientific Reports |
| title | The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer |
| title_full | The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer |
| title_fullStr | The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer |
| title_full_unstemmed | The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer |
| title_short | The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer |
| title_sort | integrative multi omics approach identifies the novel competing endogenous rna cerna network in colorectal cancer |
| url | https://doi.org/10.1038/s41598-023-46620-z |
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