Role of circular RNAs in colorectal tumor microenvironment

Ashraf, Jasni Viralippurath; Nair, Varun Sasidharan; Saleh, Reem; Elkord, Eyad

doi:10.1016/j.biopha.2021.111351

Cited by 11 publications

(9 citation statements)

References 152 publications

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“…circRNAs are aberrantly expressed in CRC and participate in a variety of biological processes, including tumor proliferation, metastasis and the remodeling of tumor microenvironment [ 37 – 39 ]. For example, circCAMSAP1 promotes CRC cells growth via the miR-328-5p/E2F1 axis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

et al. 2021

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Background Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. Methods We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC–MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. Results A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Conclusions circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

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Section: Discussionmentioning

confidence: 99%

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

et al. 2021

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“…Increasing evidence suggests that noncoding RNAs, including circRNAs, contribute to the formation of the tumor microenvironment (TME), communication between cancer cells and surrounding stromal cells (fibroblasts, immune cells, endothelial cells) and the impact of physicochemical parameters ( 57 ). Numerous studies have revealed that multiple functions of the TME may be influenced by circRNAs, not only in tumor invasiveness but also in tumor angiogenesis, epithelial to mesenchymal transition (EMT) and drug resistance ( 57 , 58 ). Thus, circRNAs may regulate the progression of TC invasion and evolution through different approaches ( Fig.…”

Section: Regulation Of Circrnas In Tcmentioning

confidence: 99%

CircRNA: A novel potential strategy to treat thyroid cancer (Review)

et al. 2021

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Thyroid cancer (TC) is the most common type of endocrine cancer. Over the last 50 years, the global incidence of TC has been increasing. The survival rate of TC is higher than that of most other types of cancer, but it depends on numerous factors, including the specific type of TC and stage of the disease. Circular RNAs (circRNAs) are a new class of long noncoding RNA with a closed loop structure that have a critical role in the complex gene regulatory network that controls the emergence of TC. The most important function of circRNAs is their ability to specifically bind to microRNAs. In addition, the biological functions of circRNAs also include interactions with proteins, regulation of the transcription of genes and acting as translation templates. Based on the characteristics of circRNAs, they have been identified as potential biomarkers for the diagnosis of tumors. In the present review, the function and significance of circRNAs and their potential clinical implications for TC were summarized. Furthermore, possible treatment approaches involving the use of mesenchymal stem cells (MSCs) and exosomes derived from MSCs as carriers to load and transport circRNAs were discussed.

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“…On the other hand, cRNAs such as circPRKDC and cirITCH act by inhibiting the activity of the β-catenin pathway[ 77 , 78 ]. The action of most of these molecules is mediated by miRNAs[ 26 , 79 ].…”

Section: Tme Factors and Conditions That Modulate The Wnt/β-catenin P...mentioning

confidence: 99%

“…For instance, circ-PRKDC participates in the development of chemoresistance to 5-FU in SW620 and SW480 cell lines by regulation of miR-375 and the Wnt/β-catenin pathway[ 77 ]. These molecules constitute a novel target for the development of alternative therapies for CRC, given their role in the communication between tumor cells and the TME and their participation in the regulation of Wnt/β-catenin[ 26 , 108 ].…”

Section: Role Of β-Catenin and The Tme In The Chemoresistance Of Crcmentioning

confidence: 99%

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Díaz¹,

Martín²,

Gentili³

2022

WJG

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Colorectal cancer (CRC) continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies. Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer, including CRC. In many subtypes of CRC, hyperactivation of the β-catenin pathway is associated with mutations of the adenomatous polyposis coli gene. However, it can also be associated with other causes. In recent years, studies of the tumor microenvironment (TME) have demonstrated its importance in the development and progression of CRC. In this tumor nest, several cell types, structures, and biomolecules interact with neoplastic cells to pave the way for the spread of the disease. Cross-communications between tumor cells and the TME are then established primarily through paracrine factors, which trigger the activation of numerous signaling pathways. Crucial advances in the field of oncology have been made in the last decade. This Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness, focusing on cross-communication between CRC cells and the TME. Through this analysis, our main objective was to increase the understanding of this complex disease considering a more global context. Since many treatments for advanced CRC fail due to mechanisms involving chemoresistance, the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

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Role of circular RNAs in colorectal tumor microenvironment

Cited by 11 publications

References 152 publications

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

CircRNA: A novel potential strategy to treat thyroid cancer (Review)

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

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