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- Kopsida, Maria, et al.
(författare)
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RhoB expression associated with chemotherapy response and prognosis in colorectal cancer
- 2024
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Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients.Materials and methods: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data.Results: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration.Conclusion: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.
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| 2. |
- Shruthi, N. R., et al.
(författare)
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Drug Repurposing in Cancer
- 2023. - 1
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Ingår i: Drug Repurposing for Emerging Infectious Diseases and Cancer. - Singapore : Springer. - 9789811953989 - 9789811953996 ; , s. 159-179
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The discovery of drug compounds has a long history in drug repurposing, notably by fortuitous findings. It has taken a new path in the creation of novel therapeutics based on existent or authorized drugs in recent years. Importantly, our knowledge of cancer biology and the related cancer hallmarks is growing. This, together with repurposing studies that use modern bioinformatics and comprehensive screening of the complete pharmacopeia, should lead to the discovery of novel medicines and targets. Furthermore, the usage of non-oncology pharmaceuticals, which make up most of our treatments, has the potential to speed up drug repurposing even further. We looked at both phenotypic-based and target-based methods of medication repurposing as well as described and assessed old non-oncology medications as prospective candidates for drug repurposing based on a broad knowledge of these principles and associated investigations of drug repurposing over the previous decade. Some of these medications successfully regulate at least one characteristic of cancer, whereas the others have a broad anticancer activity by regulating several targets through different signaling pathways, which is often brought on by various simultaneous signaling pathways. Furthermore, the emergence of computerized databases of disease gene targets, functional readouts, and clinical data encompassing inter-individual genetic variants and toxicities has allowed an alternative “big data” approach to grow at an unheard-of rate during the past decade. Here, we review the sources that are now on hand and speculate on significant upside possibilities.
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