Up-regulated Circular RNAs in Colorectal Cancer: New Entities for Therapy and Tools for Identification of Therapeutic Targets

Weidle, Ulrich H.; Nopora, Adam

doi:10.21873/cgp.20369

Cited by 4 publications

(4 citation statements)

References 223 publications

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“…Moreover, new genetic markers, such as microRNAs (miRs) and upregulated circular RNAs (circRNAs) seem to critically modify the TP53 expression levels in subsets of CRC patients (39). Two study groups reported a positive role of miR-887-3p in CRC by inhibiting cell proliferation and, in parallel, enhancing apoptotic rates due to wild type P53 activation, whereas miR-338-3p negatively affects the resistance rates to 5-fluorouracil (5-FU) in TP53 mutant CRC cases (40,41).…”

Section: Discussionmentioning

confidence: 99%

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma

NIOTIS,

DIMITROULIS,

SPYROPOULOU

et al. 2024

CDP

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Background/Aim: The tumor protein 53 (TP53) tumor suppressor protein (17p13.1) acts as a significant regulator for the cell cycle normal function. The gene is frequently mutated in colorectal adenocarcinoma (CRC) patients and is associated to poor prognosis and low response rates to chemo-targeted therapy. Our purpose was to correlate TP53 expression with Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3) and a major negative regulator in the TP53-MDM2 auto-regulatory pathway. Materials and Methods: A total of forty (n=40) colorectal adenocarcinoma (CRC) cases were included in this study. An immunohistochemistry-based assay was implemented by using anti-TP53 and anti-MDM2 antibodies in the corresponding tissue sections. Additionally, a digital image analysis assay was implemented for objectively measuring TP53/MDM2 immunostaining intensity levels. Results: TP53 protein overexpression was detected in 27/40 (67.5%), whereas MDM2 overexpression in 28/40 (70%) cases. Interestingly, in 21/40 (52.5%) cases, a combined TP53/MDM2 co-expression was detected, whereas in 6/40 (15%), a combined loss of expression was identified (overall co-expression: p=0.119). p53 overexpression was significantly correlated to grade of the examined cases (p=0.001), whereas MDM2 to stage and max diameter of the malignancies (p=0.001 and 0.024, respectively). Conclusion: TP53/MDM2 over expression is a frequent and significant genetic event in CRCs associated with an aggressive biological behavior, as a result of increased dedifferentiation grade and advanced stage/elevated tumor volume, respectively. MDM2 oncogene overactivation combined with mutated and overexpressed TP53 is observed in sub-groups of patients leading to specific gene/protein signatures – targets for personalized chemotherapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma

NIOTIS,

DIMITROULIS,

SPYROPOULOU

et al. 2024

CDP

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“…Bioinformatic-based techniques have speeded up the identification of HCC-related circ RNAs (205)(206)(207), such as circMRD27 which mediates resistance to levantinib (208). Previously we have reviewed the role of circular RNAs in breast cancer (209,210), esophageal squamous cell carcinoma (211) and colorectal cancer (212). We have extended this work to HCC and identified circRNAs which promote growth of HCC in preclinical in vivo models by sponging miRs.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

WEIDLE,

NOPORA

2023

Cancer Genomics Proteomics

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“…These issues are not discussed in further details in this review. Among the issues are pharmacokinetic CANCER GENOMICS & PROTEOMICS 21: 213-237 (2024) and pharmacodynamic aspects of the corresponding agents, immunogenicity, specificity, and delivery (15)(16)(17). The optimization process depends on the specific approach and the clinical scenario to be pursued.…”

Section: Technical Issuesmentioning

confidence: 99%

“…Physiologically, circRNAs are involved in a plethora of cellular functions (13). In cancer, circRNAs can exert oncogenic as well as tumor-suppressive functions modulating proliferation, angiogenesis, migration, and metastasis (14)(15)(16)(17). In addition, circRNAs can act as scaffolds or sponges for proteins, regulate transcription, interact with RNAs, modulate translation and, in some cases, they can encode proteins (18).…”

mentioning

confidence: 99%

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in PreclinicalIn VivoModels: Identification of Targets and New Modalities for Therapeutic Intervention

WEIDLE,

BIRZELE

2024

Cancer Genomics Proteomics

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Epithelial ovarian cancer (EOC) is associatedwith a dismal prognosis due to development of resistance to chemotherapy and metastasis in the peritoneal cavity and distant organs. In order to identify new targets and treatment modalities we searched the literature for up-and and downregulated circRNAs with efficacy in preclinical EOC-related in vivo systems. Our search yielded circRNAs falling into the following categories: cisplatin and paclitaxel resistance, transmembrane receptors, secreted factors, transcription factors, RNA splicing and processing factors, RAS pathwayrelated components, proteolysis and cell-cycle regulation, signaling-related proteins, and circRNAs regulating proteins in additional categories. These findings can be potentially translated by validation and manipulation of the corresponding targets, inhibition of circRNAs with antisense oligonucleotides (ASO), small interfering RNAs (siRNA) or small hairpin RNA (shRNA) or by reconstituting their activity.The incidence of ovarian cancer (OC) in the USA is 22,000 cases per year and 14,000 deaths, and 29,000 deaths in Europe (1). The vast majority are epithelial ovarian cancers (EOC). This type of tumor is typically treated with a combination of surgery and chemotherapy, which often includes cisplatin (DDP) and paclitaxel (PTX). An exciting development was the treatment of homologous recombination-deficient ovarian tumors with breast cancer antigen (BRCA) mutations or deletions with poly-ADP-ribose polymerase (PARP) inhibitors (2). Three PARP inhibitors (olaparib, rucaparib and niraparib) have been approved for the treatment of OCs in different clinical settings. In addition, anti-angiogenic therapy with Bevacizumab was approved (3). Nevertheless, recurrence due to resistance mechanisms is commonly observed and significantly impairs the therapeutic benefit of treatment (4). Epithelial ovarian cancer (EOC) gains a growth advantage due to interactions with fat cells, mesothelial cells, and cancerassociated fibroblasts. These interactions enhance the activation of pathways that support its growth (5-7). Also, its dissemination in ascites fluid and formation of nodules in the peritoneum are a unique mechanism of metastasis hampering therapeutic intervention (8, 9). Immunotherapy with checkpoint inhibitors such as Pembrolizumab has shown limited success (10). Diverse mechanisms of immune escape in a tumorlocation specific manner have been observed (11). Taken together, there is a tremendous medical need for identification of new targets and modalities for treatment of OC. Therefore, we searched the literature for circular RNAs (circRNAs) that are up-or down-regulated in EOC and upon their modulation exhibit efficacy in preclinical in vivo models of EOC. Circular RNA in CancercircRNA can be generated during mRNA processing by intramolecular mRNA pairing followed by circularization, RNA-213

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Up-regulated Circular RNAs in Colorectal Cancer: New Entities for Therapy and Tools for Identification of Therapeutic Targets

Abstract: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

Cited by 4 publications

References 223 publications

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in PreclinicalIn VivoModels: Identification of Targets and New Modalities for Therapeutic Intervention

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