| 1. |
- Ganesan, Harsha, et al.
(författare)
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Mucinous Colorectal Cancer Oxidative Stress and Therapeutic MicroRNAs
- 2022
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Ingår i: Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. - Singapore : Springer. - 9789811654213 - 9789811654220 ; , s. 1-18
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Bokkapitel (refereegranskat)abstract
- Colorectal Cancer (CRC) is the third most leading cause of cancer related death worldwide and has a diverse clinical etiology. Mounting evidences has shown that CRC, in its rare yet lethal form as mucinous adenocarcinoma. Has led to poor prognosis and eventual complexity in the treatment. This subcategory of CRC characteristically secrete mucin hence, they are histologically identified based on the presence of mucin in CRC. In this context, the current article aims to provide a detailed overview and understanding of the underlying molecular mechanisms governing mucinous cancer onset and progression. We elaborate on the role of different pathways and molecular targets including microsatellite instability (MSI), chromosome instability (CIN) and CpG island methylator phenotype (CIMP), oncogenes such as KRAS, BRAF, p53 and p21 on mucinous CRC. The mucin genes, specifically MUC1, MUC4 and few other variants of the gel-secreted, transmembrane form of CRC play a vital role in the disease development. This makes the miRNA-mediated mucin regulations an exceptionally obliging aid in mucinous CRC understanding. The miRNAs discussed in context include miR-205, miR-373 and miR-124a to name a few. We further discuss the existing therapeutic strategies used to treat this variant of CRC. These diagnostic tools could help in the rapid identification and treatment of the disease.
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| 2. |
- Ganesan, Harsha, et al.
(författare)
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RNA-Interference-Mediated miR-122-Based Gene Regulation in Colon Cancer, a Structural In Silico Analysis
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:23
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Tidskriftsartikel (refereegranskat)abstract
- The role of microRNA 122 (miR-122) in colorectal cancer (CRC) has not been widely investigated. In the current study, we aimed to identify the prominent gene and protein interactors of miR122 in CRC. Based on their binding affinity, these targets were chosen as candidate genes for the creation of miR122-mRNA duplexes. Following this, we examined the miRNA-mediated silencing mechanism using the gene-silencing complex protein Argonaute (AGO). Public databases, STRING, and GeneMANIA were utilized to identify major proteins and genes interacting with miR-122. DAVID, PANTHER, UniProt, FunRich, miRwalk, and KEGG were used for functional annotation, pathway enrichment, binding affinity analysis, and expression of genes in different stages of cancer. Three-dimensional duplexes of hub genes and miR-122 were created using the RNA composer, followed by molecular interaction analysis using molecular docking with the AGO protein. We analyzed, classified, and scrutinized 93 miR-122 interactors using various bioinformatic approaches. A total of 14 hub genes were categorized as major interactors of miR-122. The study confirmed the role of various experimentally documented miR-122 interactors such as MTDH (Q86UE4), AKT1 (P31749), PTPN1 (P18031), MYC (P01106), GSK3B (P49841), RHOA (P61586), and PIK3CG (P48736) and put forth several novel interactors, with AKT3 (Q9Y243), NCOR2 (Q9Y618), PIK3R2 (O00459), SMAD4 (P61586), and TGFBR1 (P36897). Double-stranded RNA duplexes of the strongest interactors were found to exhibit higher binding affinity with AGO. In conclusions, the study has explored the role of miR-122 in CRC and has identified a closely related group of genes influencing the prognosis of CRC in multiple ways. Further, these genes prove to be targets of gene silencing through RNA interference and might serve as effective therapeutic targets in understanding and treating CRC.
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| 3. |
- 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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| 4. |
- Sriramulu, Sushmitha, et al.
(författare)
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Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types : A Concise Review
- 2021
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:6
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Forskningsöversikt (refereegranskat)abstract
- Tumor breakthrough is driven by genetic or epigenetic variations which assist in initiation, migration, invasion and metastasis of tumors. Astrocyte elevated gene-1 (AEG-1) protein has risen recently as the crucial factor in malignancies and plays a potential role in diverse complex oncogenic signaling cascades. AEG-1 has multiple roles in tumor growth and development and is found to be involved in various signaling pathways of: (i) Ha-ras and PI3K/AKT; (ii) the NF-kappa B; (iii) the ERK or mitogen-activated protein kinase and Wnt or beta-catenin and (iv) the Aurora-A kinase. Recent studies have confirmed that in all the hallmarks of cancers, AEG-1 plays a key functionality including progression, transformation, sustained angiogenesis, evading apoptosis, and invasion and metastasis. Clinical studies have supported that AEG-1 is actively intricated in tumor growth and progression which includes esophageal squamous cell, gastric, colorectal, hepatocellular, gallbladder, breast, prostate and non-small cell lung cancers, as well as renal cell carcinomas, melanoma, glioma, neuroblastoma and osteosarcoma. Existing studies have reported that AEG-1 expression has been induced by Ha-ras through intrication of PI3K/AKT signaling. Conversely, AEG-1 also activates PI3K/AKT pathway and modulates the defined subset of downstream target proteins via crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling cascade which further plays a crucial role in metastasis. Thus, AEG-1 may be employed as a biomarker to discern the patients of those who are likely to get aid from AEG-1-targeted medication. AEG-1 may play as an effective target to repress tumor development, occlude metastasis, and magnify the effectiveness of treatments. In this review, we focus on the molecular mechanism of AEG-1 in the process of carcinogenesis and its involvement in regulation of crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling. We also highlight the multifaceted functions, expression, clinicopathological significance and molecular inhibitors of AEG-1 in various cancer types.
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