Extracellular Vesicles-ceRNAs as Ovarian Cancer Biomarkers: Looking into circRNA-miRNA-mRNA Code

Cammarata, Giuseppe; Barraco, Nadia; Giusti, Ilaria; Gristina, Valerio; Dolo, Vincenza; Taverna, Simona

doi:10.3390/cancers14143404

Cited by 22 publications

(14 citation statements)

References 196 publications

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“…It is worth mentioning that circRNAs derived from ovarian cells in extracellular vesicles play a crucial role in regulating gene expression, affecting ovarian cell growth, function, and the development of ovarian diseases [76,77]. Future research will provide new insights into diagnosis and treatment methods.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Differentially Expressed Circular RNAs Associated with Fecundity in the Sheep Hypothalamus with Different FecB Genotypes

He,

Chen,

Guo

et al. 2024

Animals

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Circular RNAs (circRNAs) are a specific type of noncoding RNA, and some have defined roles in cellular and biological processes. However, little is known about the role of circRNAs in follicular development in sheep with FecB (fecundity Booroola) mutations. Here, the expression profiles of circRNAs were investigated using RNA sequencing (RNA-seq) in the follicular phase (F) and the luteal phase (L) of FecB mutant homozygous (BB) and wild-type (WW) Small Tail Han sheep. A total of 38,979 circRNAs were identified, and 314, 343, 336, and 296 of them were differentially expressed (DE) between BB_F and BB_L, WW_F and WW_L, BB_F and WW_F, and BB_L and WW_L, respectively. The length, type, and chromosome distribution of the circRNAs and the expression characteristic between the circRNAs and their host genes in the sheep hypothalamus were ascertained. Enrichment analysis showed that the host genes of DE circRNAs in the follicular and luteal phases were annotated to MAPK, gap junctions, progesterone-mediated oocyte maturation, oocyte meiosis, and other hormone-related signaling pathways, and the different FecB genotypes were annotated to the gap junctions, circadian entrainment, MAPK, and other hormone-related signaling pathways. The competing endogenous RNA network prediction revealed that the 129 target miRNAs might be bound to 336 DE circRNAs. oar_circ_0000523 and oar_circ_0028984, which were specifically expressed during the follicular phase in the BB genotype sheep, probably acted as miRNA sponges involved in the regulation of LH synthesis and secretion. This study reveals the expression profiles and characterization of circRNAs at two phases of follicular development considering different FecB genotypes, thereby providing an improved understanding of the roles of circRNAs in the sheep hypothalamus and their involvement in follicular development and ovulation.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Differentially Expressed Circular RNAs Associated with Fecundity in the Sheep Hypothalamus with Different FecB Genotypes

He,

Chen,

Guo

et al. 2024

Animals

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“…By integrating circRNAs and piRNAs into combination therapies, we can potentially harness their ability to fine-tune immune responses and target multiple pathways involved in tumor evasion. 178,180,181 This approach not only exemplifies the complexity of tumor-immune interactions but also emphasizes the need for personalized therapeutic strategies that consider the individual tumor microenvironment and the specific ncRNA profiles of patients.…”

Section: Dovepressmentioning

confidence: 99%

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

Han,

Rao,

Zhou

et al. 2024

IJN

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The utilization of PD-1/PD-L1 inhibitors marks a significant advancement in cancer therapy. However, the efficacy of monotherapy is still disappointing in a substantial subset of patients, necessitating the exploration of combinational strategies. Emerging from the promising results of the KEYNOTE-942 trial, RNA-based therapies, particularly circRNAs and piRNAs, have distinguished themselves as innovative sensitizers to immune checkpoint inhibitors (ICIs). These non-coding RNAs, notable for their stability and specificity, were once underrecognized but are now known for their crucial roles in regulating PD-L1 expression and bolstering anti-cancer immunity. Our manuscript offers a comprehensive analysis of selected circRNAs and piRNAs, elucidating their immunomodulatory effects and mechanisms, thus underscoring their potential as ICIs enhancers. In conjunction with the recent Nobel Prize-awarded advancements in mRNA vaccine technology, our review highlights the transformative implications of these findings for cancer treatment. We also discuss the prospects of circRNAs and piRNAs in future therapeutic applications and research. This study pioneers the synergistic application of circRNAs and piRNAs as novel sensitizers to augment PD-1/PD-L1 inhibition therapy, demonstrating their unique roles in regulating PD-L1 expression and modulating immune responses. Our findings offer a groundbreaking approach for enhancing the efficacy of cancer immunotherapy, opening new avenues for treatment strategies. This abstract aims to encapsulate the essence of our research and the burgeoning role of these non-coding RNAs in enhancing PD-1/ PD-L1 inhibition therapy, encouraging further investigation into this promising field.

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“…Given that these proteins are primarily found in tumor-derived exosomes and have a strong influence on the progression of OC, they can be considered promising targets for the treatment of OC as well as possible prognostic markers of the disease [26,54,57,58]. In addition, the proteins ZBED2, ZBTB20, ABCC3, and UHMK1, which are involved in cell cycle regulation and drug transport, were found in exosomes derived from ascitic fluid [59].…”

Section: Proteome Of Exosomesmentioning

confidence: 99%

Exosomal Cargo in Ovarian Cancer Dissemination

Dzhugashvili,

Tamkovich

2023

CIMB

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Ovarian cancer (OC) has the highest mortality rate among all gynecologic cancers and is characterized by early peritoneal spread. The growth and development of OC are associated with the formation of ascitic fluid, creating a unique tumor microenvironment. Understanding the mechanisms of tumor progression is crucial in identifying new diagnostic biomarkers and developing novel therapeutic strategies. Exosomes, lipid bilayer vesicles measuring 30–150 nm in size, are known to establish a crucial link between malignant cells and their microenvironment. Additionally, the confirmed involvement of exosomes in carcinogenesis enables them to mediate the invasion, migration, metastasis, and angiogenesis of tumor cells. Functionally active non-coding RNAs (such as microRNAs, long non-coding RNAs, circRNAs), proteins, and lipid rafts transported within exosomes can activate numerous signaling pathways and modify gene expression. This review aims to expand our understanding of the role of exosomes and their contents in OC carcinogenesis processes such as epithelial-mesenchymal transition (EMT), angiogenesis, vasculogenic mimicry, tumor cell proliferation, and peritoneal spread. It also discusses the potential for utilizing exosomal cargo to develop novel “liquid biopsy” biomarkers for early OC diagnosis.

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Extracellular Vesicles-ceRNAs as Ovarian Cancer Biomarkers: Looking into circRNA-miRNA-mRNA Code

Cited by 22 publications

References 196 publications

Transcriptomic Analysis Reveals Differentially Expressed Circular RNAs Associated with Fecundity in the Sheep Hypothalamus with Different FecB Genotypes

Transcriptomic Analysis Reveals Differentially Expressed Circular RNAs Associated with Fecundity in the Sheep Hypothalamus with Different FecB Genotypes

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

Exosomal Cargo in Ovarian Cancer Dissemination

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