<scp>circPVT1</scp> and <scp><i>PVT1/AKT3</i></scp> show a role in cell proliferation, apoptosis, and tumor subtype‐definition in small cell lung cancer

Tolomeo, Doron; Traversa, Debora; Venuto, Santina; Ebbesen, Karoline K; García-Rodríguez, Juan L.; Tamma, Grazia; Ranieri, Marianna; Simonetti, Giorgia; Ghetti, Martina; Paganelli, Matteo; Visci, Grazia; Liso, Arcangelo; Kok, Klaas; Muscarella, Lucia Anna; Fabrizio, Federico Pio; Frassanito, Maria Antonia; Lamanuzzi, Aurelia; Saltarella, Ilaria; Solimando, Antonio Giovanni; Fatica, Alessandro; Ianniello, Zaira; Marsano, Renè Massimiliano; Palazzo, Antonio J.; Azzariti, Amalia; Longo, Vito; Tommasi, Stefania; Galetta, Domenico; Catino, Annamaria; Zito, Alfredo; Mazza, Tommaso; Napoli, Alessandro; Martinelli, Giovanni; Kjems, Jørgen; Kristensen, Lasse Sommer; Vacca, Angelo; Storlazzi, Clelia Tiziana

doi:10.1002/gcc.23121

Cited by 11 publications

(8 citation statements)

References 84 publications

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“…Further experiments show that circPVT1 inhibited the degradation of AEG-1 (Astrocyte Elevated Gene 1) by binding to miRNA-30b-5p. The oncogene AEG-1 was demonstrated that it could regulate the expression of genes associated with breast cancer malignant progression [13]. Our data suggest that circPVT1 is a key regulator of AEG-1 in the breast cancer and might be a novel biomarker target for breast cancer diagnosis and treatment.…”

Section: Discussionmentioning

confidence: 68%

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Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Li,

et al. 2023

Preprint

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Background: Circular RNA PVT1 (circPVT1) has been reported to be a vital modulator in tumorigenesis. However, the detailed regulatory mechanism of circPVT1 in breast cancer (BC) remains largely unclear. Objective: This research is to explore the mechanisms of circPVT1 in breast cancer from different perspectives. Methods: In this work, the expressions of circPVT1 and microRNA-30b-5p (miR-30b-5p) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cell lines. The Kaplan-Meierk was adopted to compare disease free survival (DFS) and overall (OS). BC cell lines MDA-MB-231and MCF-7 cell lines were chosen for the following assays. After circPVT1 was depleted, CCK-8 and Transwell assays were performed to examine the cell viability and invasive capacity. Astrocyte elevated gene 1 (AEG-1) protein level was measured by western blot. The competitive endogenous RNA molecular mechanism among circPVT1, miR-30b-5p and AEG-1 was verified by bioinformatics analysis, luciferase-reporter gene assay. Results: In the present study, it was revealed that circPVT1 expression was remarkably evaluated in BC tissues and cell lines than that in the corresponding control group. The Kaplan-Meier analysis shown that high circPVT1 expression had a significantly poorer survival prognosis than those with low circPVT1 expression in DFS (χ2 = 7.174, P = 0.007) and OS (χ2 = 3.946, P = 0.047). CircPVT1 positively regulated the proliferation, migration and invasion progression of BC cells. Besides, miR-30b-5p was identified as a target of circPVT1, and AEG-1 was identified as a target of miR-30b-5p. The depletion of circPVT1 promoted the expression of miR-30b-5p and suppressed AEG-1 expression. Moreover, simultaneous inhibition of miR-30b-5p expression in the circPVT1 knockout group could reverse the inhibition of AEG-1 expression. Conclusion: In conclusion, our results indicate circPVT1 regulates AEG-1 expression by competitively binding to endogenous miR-30b-5p in breast cancer cells. CircPVT1 promoted AEG-1 expression by negatively regulating miR-30b-5p expression to enhance the cell viability, migration, and invasion progression of BC cells. Our results reveal a new molecular therapy target for breast cancer.

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Section: Discussionmentioning

confidence: 68%

“…CircPVT1 is located on chromosome 8q24 and plays a carcinogenic role in a variety of cancers, including lung cancer, head and neck cancer, and oral squamous cell carcinoma [5,6,7]. Several studies found circPVT1 might exert an oncogenic effect in cancer cells by stabilizing c-Myc protein expression [8,9].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Li,

et al. 2023

Preprint

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“…However, we have recently demonstrated an oncogenic role in vitro for the PVT1::AKT3 chimera, transcribed from a fusion gene mapping on an HSR in the MYC -amplified SCLC cell line GLC1HSR [ 22 ]. Indeed, its silencing decreased cell proliferation and increased apoptosis [ 113 ].…”

Section: Methods and Bioinformatic Tools To Detect Genomic Amplificat...mentioning

confidence: 99%

Advancements in Focal Amplification Detection in Tumor/Liquid Biopsies and Emerging Clinical Applications

Arshadi,

Tolomeo,

Venuto

et al. 2023

Genes

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Focal amplifications (FAs) are crucial in cancer research due to their significant diagnostic, prognostic, and therapeutic implications. FAs manifest in various forms, such as episomes, double minute chromosomes, and homogeneously staining regions, arising through different mechanisms and mainly contributing to cancer cell heterogeneity, the leading cause of drug resistance in therapy. Numerous wet-lab, mainly FISH, PCR-based assays, next-generation sequencing, and bioinformatics approaches have been set up to detect FAs, unravel the internal structure of amplicons, assess their chromatin compaction status, and investigate the transcriptional landscape associated with their occurrence in cancer cells. Most of them are tailored for tumor samples, even at the single-cell level. Conversely, very limited approaches have been set up to detect FAs in liquid biopsies. This evidence suggests the need to improve these non-invasive investigations for early tumor detection, monitoring disease progression, and evaluating treatment response. Despite the potential therapeutic implications of FAs, such as, for example, the use of HER2-specific compounds for patients with ERBB2 amplification, challenges remain, including developing selective and effective FA-targeting agents and understanding the molecular mechanisms underlying FA maintenance and replication. This review details a state-of-the-art of FA investigation, with a particular focus on liquid biopsies and single-cell approaches in tumor samples, emphasizing their potential to revolutionize the future diagnosis, prognosis, and treatment of cancer patients.

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“…Consistently, circPVT1 was also found upregulated in several cancers, such as bladder cancer, oral squamous cell carcinoma, and small cell lung cancer, highlighting its relevance in cancer progression. [ 368 – 370 ] . Another circRNA involved in the regulation of metastasis in different tumor types, including OS, is circUBAP2 [ 371 – 374 ].…”

Section: Cernets Involving Circrnasmentioning

confidence: 99%

Osteosarcoma in a ceRNET perspective

Mosca,

Alessio,

Di Paola

et al. 2024

J Biomed Sci

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Osteosarcoma (OS) is the most prevalent and fatal type of bone tumor. It is characterized by great heterogeneity of genomic aberrations, mutated genes, and cell types contribution, making therapy and patients management particularly challenging. A unifying picture of molecular mechanisms underlying the disease could help to transform those challenges into opportunities.This review deeply explores the occurrence in OS of large-scale RNA regulatory networks, denominated “competing endogenous RNA network” (ceRNET), wherein different RNA biotypes, such as long non-coding RNAs, circular RNAs and mRNAs can functionally interact each other by competitively binding to shared microRNAs. Here, we discuss how the unbalancing of any network component can derail the entire circuit, driving OS onset and progression by impacting on cell proliferation, migration, invasion, tumor growth and metastasis, and even chemotherapeutic resistance, as distilled from many studies. Intriguingly, the aberrant expression of the networks components in OS cells can be triggered also by the surroundings, through cytokines and vesicles, with their bioactive cargo of proteins and non-coding RNAs, highlighting the relevance of tumor microenvironment. A comprehensive picture of RNA regulatory networks underlying OS could pave the way for the development of innovative RNA-targeted and RNA-based therapies and new diagnostic tools, also in the perspective of precision oncology.

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circPVT1 and PVT1/AKT3 show a role in cell proliferation, apoptosis, and tumor subtype‐definition in small cell lung cancer

Cited by 11 publications

References 84 publications

Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Advancements in Focal Amplification Detection in Tumor/Liquid Biopsies and Emerging Clinical Applications

Osteosarcoma in a ceRNET perspective

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