The Role of Circular RNAs in Therapy Resistance of Patients With Solid Tumors

Papatsirou, Maria; Artemaki, Pinelopi I; Scorilas, Andreas; Kontos, Christos K.

doi:10.2217/pme-2020-0103

Cited by 43 publications

(37 citation statements)

References 140 publications

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“…In several instances, the involvement of circRNAs in the deregulation of signal transduction has been evidenced, supporting the key role of circRNAs in cancer initiation, progression, metastasis, stemness, and resistance to therapy [ 35 ]. More specifically, circRNAs can regulate the cell cycle by exerting their sponging ability; for instance, circ-ZNF292 inhibits cell proliferation and promotes apoptosis of hepatocellular carcinoma cells by regulating the WNT/β-catenin pathway [ 36 ].…”

Section: Functions Of Circrnas and Their Involvement In Signal Transductionmentioning

confidence: 98%

“…Considering the multiple biological functions of circRNAs, it is not surprising that numerous researchers have focused on elucidating their distinct properties. For this reason, their implication in the regulation of aberrant signaling, cancer onset, progression, and therapy resistance has repeatedly been demonstrated [ 16 , 35 ], and the most promising areas for future research are shown in Figure 7 . The immense potential of highly expressed circRNAs as novel, non-invasive biomarkers has righteously kept them in the spotlight; circulating circRNAs are enriched in body fluids, such as blood, saliva, plasma, and serum, and there are several circRNAs found in exosomes that can affect the tumor microenvironment and malignancy of cancer cells [ 122 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

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Circular RNAs: Emerging Regulators of the Major Signaling Pathways Involved in Cancer Progression

Papatsirou

Artemaki

Karousi

et al. 2021

Cancers

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Signal transduction is an essential process that regulates and coordinates fundamental cellular processes, such as development, immunity, energy metabolism, and apoptosis. Through signaling, cells are capable of perceiving their environment and adjusting to changes, and most signaling cascades ultimately lead to alterations in gene expression. Circular RNAs (circRNAs) constitute an emerging type of endogenous transcripts with regulatory roles and unique properties. They are stable and expressed in a tissue-, cell-, and developmental stage-specific manner, while they are involved in the pathogenesis of several diseases, including cancer. Aberrantly expressed circRNAs can mediate cancer progression through regulation of the activity of major signaling cascades, such as the VEGF, WNT/β-catenin, MAPK, PI3K/AKT, and Notch signaling pathways, as well as by interfering with signaling crosstalk. Deregulated signaling can then function to induce angiogenesis, promote invasion, migration, and metastasis, and, generally, modulate the hallmarks of cancer. In this review article, we summarize the most recently described and intriguing cases of circRNA-mediated signaling regulation that are involved in cancer progression, and discuss the biomarker potential of circRNAs, as well as future therapeutic applications.

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Section: Functions Of Circrnas and Their Involvement In Signal Transductionmentioning

confidence: 98%

Section: Future Perspectivesmentioning

confidence: 99%

Circular RNAs: Emerging Regulators of the Major Signaling Pathways Involved in Cancer Progression

Papatsirou

Artemaki

Karousi

et al. 2021

Cancers

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“…circRNAs modulate gene expression by various mechanisms, including functioning as miRNA sponges, RNA-binding protein (RBP) sponges, transcription regulators, and templates for translating peptides [ 37 , 43 , 44 ]. ciRS-7 (also known as CDR1as ), the first miRNA sponge to be identified, is well known for sponging miR-7 [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Sp1-Mediated circRNA circHipk2 Regulates Myogenesis by Targeting Ribosomal Protein Rpl7

Yan

Yang

Fan

et al. 2021

Genes

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Circular RNAs (circRNAs) represent a class of covalently closed single-stranded RNA molecules that are emerging as essential regulators of various biological processes. The circRNA circHipk2 originates from exon 2 of the Hipk2 gene in mice and was reported to be involved in acute promyelocytic leukemia and myocardial injury. However, the functions and mechanisms of circHipk2 in myogenesis are largely unknown. Here, to deepen our knowledge about the role of circHipk2, we studied the expression and function of circHipk2 during skeletal myogenesis. We found that circHipk2 was mostly distributed in the cytoplasm, and dynamically and differentially expressed in various myogenesis systems in vitro and in vivo. Functionally, overexpression of circHipk2 inhibited myoblast proliferation and promoted myotube formation in C2C12 cells, whereas the opposite effects were observed after circHipk2 knockdown. Mechanistically, circHipk2 could directly bind to ribosomal protein Rpl7, an essential 60S preribosomal assembly factor, to inhibit ribosome translation. In addition, we verified that transcription factor Sp1 directly bound to the promoter of circHipk2 and affected the expression of Hipk2 and circHipk2 in C2C12 myoblasts. Collectively, these findings identify circHipk2 as a candidate circRNA regulating ribosome biogenesis and myogenesis proliferation and differentiation.

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“…In the era of individualized and precision medicine, robust molecular markers are required to ameliorate therapeutic decisions [34,35]. The integration of diagnostic, prognostic, and predictive molecular markers revolutionizes the field of modern oncology by providing tailored therapeutic management [36][37][38]. As already mentioned, miRNAs regulate gene expression at the transcriptional and post-transcriptional levels.…”

Section: Discussionmentioning

confidence: 99%

A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

Παπανώτα

Tsiakanikas

Kontos

et al. 2021

Cancers

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Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA–based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM.

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The Role of Circular RNAs in Therapy Resistance of Patients With Solid Tumors

Cited by 43 publications

References 140 publications

Circular RNAs: Emerging Regulators of the Major Signaling Pathways Involved in Cancer Progression

Circular RNAs: Emerging Regulators of the Major Signaling Pathways Involved in Cancer Progression

Sp1-Mediated circRNA circHipk2 Regulates Myogenesis by Targeting Ribosomal Protein Rpl7

A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

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