Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment
Ganoderic acid Me (GA-Me) is a natural bioactive compound derived from Ganoderma lucidum. Our present results suggested that GA-Me inhibited proliferation, induced DNA fragmentation and significantly activated caspase-9 and caspase-3 in HCT116 cells. As shown in our previous studies, GA-Me targets s...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.833375/full |
| _version_ | 1817991417932283904 |
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| author | Nianhong Chen Nianhong Chen Nianhong Chen Guoqing Wan Guoqing Wan Xiaobin Zeng Xiaobin Zeng |
| author_facet | Nianhong Chen Nianhong Chen Nianhong Chen Guoqing Wan Guoqing Wan Xiaobin Zeng Xiaobin Zeng |
| author_sort | Nianhong Chen |
| collection | DOAJ |
| description | Ganoderic acid Me (GA-Me) is a natural bioactive compound derived from Ganoderma lucidum. Our present results suggested that GA-Me inhibited proliferation, induced DNA fragmentation and significantly activated caspase-9 and caspase-3 in HCT116 cells. As shown in our previous studies, GA-Me targets several genes to prevent cancer, including colorectal cancer (CRC). Thus, we hypothesized that GA-Me might be a multitarget ligand against cancer. However, its exact mechanism in CRC remains unclear. Here, whole-transcriptome sequencing was employed to assess the long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) profiles of GA-Me-treated HCT116 cells. In total, 1572 differentially expressed (DE) lncRNAs, 123 DEcircRNAs, 87 DEmiRNAs, and 1508 DEmRNAs were identified. DCBLD2 and RAPGEF5 were validated as two core mRNAs in the DElncRNA, DEcircRNA, and DEmiRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological functions and potential mechanisms of TCONS-00008997, XR-925056.2, circRNA-07908, hsa-miR-100-3p, hsa-miR-1257, hsa-miR-3182, NAV3, ADAM20, and STARD4, which were altered after GA-Me treatment. The regulatory relationships of the XR-925056.2-hsa-miR-3182-NAV3/ADAM20/STARD4, circRNA-07908|Chr22:38986298-39025349-hsa-miR-3182-NAV3/ADAM20, ENST00000414039/ENST00000419190-novel874_mature-MMP9 and circRNA-00314|Chr1:35470863-35479212/circRNA-05460|Chr17:72592203-72649268-novel874_mature-MMP9 immune-regulatory networks involved both noncoding RNAs (ncRNAs) and mRNAs. Molecular docking studies showed that Zn2+ and the His201, His205, His211, Glu202, and Ala165 residues of MMP2 contributed to its high affinity for GA-Me. Zn2+ and the Glu402 and Gly186 residues of MMP9 are important for its interaction with GA-Me. Our results suggested and confirmed that GA-Me is a potential multitarget lead compound for CRC treatment with unique polypharmacological advantages. |
| first_indexed | 2024-04-14T01:12:59Z |
| format | Article |
| id | doaj.art-5712ea7d583d4ef6be5169a0da223a7c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T01:12:59Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-5712ea7d583d4ef6be5169a0da223a7c2022-12-22T02:20:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.833375833375Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer TreatmentNianhong Chen0Nianhong Chen1Nianhong Chen2Guoqing Wan3Guoqing Wan4Xiaobin Zeng5Xiaobin Zeng6Center Lab of Longhua Branch and Department of Infectious Disease, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen,ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Medicine School of Shenzhen University, Shenzhen, ChinaLaboratory of Signal Transduction, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, United StatesCenter Lab of Longhua Branch and Department of Infectious Disease, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen,ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Medicine School of Shenzhen University, Shenzhen, ChinaCenter Lab of Longhua Branch and Department of Infectious Disease, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen,ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Medicine School of Shenzhen University, Shenzhen, ChinaGanoderic acid Me (GA-Me) is a natural bioactive compound derived from Ganoderma lucidum. Our present results suggested that GA-Me inhibited proliferation, induced DNA fragmentation and significantly activated caspase-9 and caspase-3 in HCT116 cells. As shown in our previous studies, GA-Me targets several genes to prevent cancer, including colorectal cancer (CRC). Thus, we hypothesized that GA-Me might be a multitarget ligand against cancer. However, its exact mechanism in CRC remains unclear. Here, whole-transcriptome sequencing was employed to assess the long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) profiles of GA-Me-treated HCT116 cells. In total, 1572 differentially expressed (DE) lncRNAs, 123 DEcircRNAs, 87 DEmiRNAs, and 1508 DEmRNAs were identified. DCBLD2 and RAPGEF5 were validated as two core mRNAs in the DElncRNA, DEcircRNA, and DEmiRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological functions and potential mechanisms of TCONS-00008997, XR-925056.2, circRNA-07908, hsa-miR-100-3p, hsa-miR-1257, hsa-miR-3182, NAV3, ADAM20, and STARD4, which were altered after GA-Me treatment. The regulatory relationships of the XR-925056.2-hsa-miR-3182-NAV3/ADAM20/STARD4, circRNA-07908|Chr22:38986298-39025349-hsa-miR-3182-NAV3/ADAM20, ENST00000414039/ENST00000419190-novel874_mature-MMP9 and circRNA-00314|Chr1:35470863-35479212/circRNA-05460|Chr17:72592203-72649268-novel874_mature-MMP9 immune-regulatory networks involved both noncoding RNAs (ncRNAs) and mRNAs. Molecular docking studies showed that Zn2+ and the His201, His205, His211, Glu202, and Ala165 residues of MMP2 contributed to its high affinity for GA-Me. Zn2+ and the Glu402 and Gly186 residues of MMP9 are important for its interaction with GA-Me. Our results suggested and confirmed that GA-Me is a potential multitarget lead compound for CRC treatment with unique polypharmacological advantages.https://www.frontiersin.org/articles/10.3389/fonc.2022.833375/fullganoderic acid Mecolorectal cancerwhole-transcriptomic analysisnetwork analysismolecular docking studyprotein–protein interaction network |
| spellingShingle | Nianhong Chen Nianhong Chen Nianhong Chen Guoqing Wan Guoqing Wan Xiaobin Zeng Xiaobin Zeng Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment Frontiers in Oncology ganoderic acid Me colorectal cancer whole-transcriptomic analysis network analysis molecular docking study protein–protein interaction network |
| title | Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment |
| title_full | Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment |
| title_fullStr | Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment |
| title_full_unstemmed | Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment |
| title_short | Integrated Whole-Transcriptome Profiling and Bioinformatics Analysis of the Polypharmacological Effects of Ganoderic Acid Me in Colorectal Cancer Treatment |
| title_sort | integrated whole transcriptome profiling and bioinformatics analysis of the polypharmacological effects of ganoderic acid me in colorectal cancer treatment |
| topic | ganoderic acid Me colorectal cancer whole-transcriptomic analysis network analysis molecular docking study protein–protein interaction network |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.833375/full |
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