Insights into the Evolving Roles of Circular RNAs in Cancer

Harper, Katherine L.; Mottram, Timothy J.; Whitehouse, Adrian

doi:10.3390/cancers13164180

Cited by 19 publications

(12 citation statements)

References 66 publications

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“…The above characteristics make circRNAs have the potential to become biomarkers, so circRNAs have attracted the attention of many researchers. As reported, the abnormal expression of circRNAs was related to the pathogenesis of many diseases [4,10]. CircRNAs could interfere with disease progression by affecting various biological functions such as cell proliferation, metastasis, metabolism and chemotherapy resistance [6,24,25].…”

Section: Introductionmentioning

confidence: 89%

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

et al. 2022

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Background Circ-NT5C2 has been confirmed to be highly expressed and associated to the progression of osteosarcoma (OS). However, the behind mechanism of circ-NT5C2 involvement in OS remains unclear. Methods The expression of circ-NT5C2, miR-488-3p and FZD4 was measured by quantitative real-time PCR, and the protein expression of E-cadherin, N-cadherin and FZD4 was detected by western blot. Cell counting kit 8 assay, colony formation assay and 5-ethynyl-2-deoxyuridine assay were performed to assess the cell proliferation. The cell apoptosis was measured by flow cytometry and Caspase3/Caspase9 Activity Assay Kits. Cell migration and invasion were detected by transwell assay. Dual-luciferase reporter assay and RIP assay were carried out to determine the binding relation among circ-NT5C2, miR-488-3p and FZD4. Animal experiment and immunohistochemistry analysis were conducted to explore the role of circ-NT5C2 in tumor growth in vivo. Results Comparing with controls, the expression of circ-NT5C2 and FZD4 was upregulated and miR-488-3p expression was downregulated in OS tumor tissues and cells. Circ-NT5C2 overexpression facilitated the cell proliferation and motility and induced cell apoptosis of OS cells, whereas circ-NT5C2 knockdown had the opposite effect. Besides, we also found and confirmed that circ-NT5C2 regulated cell malignant behaviors via modulating miR-488-3p/FZD4 axis in OS. Moreover, circ-NT5C2 silencing repressed the growth of xenografts in vivo. Conclusion Circ-NT5C2 upregulated FZD4 expression via sponging miR-488-3p, thus facilitating cell malignant behaviors in OS.

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Section: Introductionmentioning

confidence: 89%

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

et al. 2022

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“…Tumor cells can secrete 10 times more exosomes than other cells [119]. In the serum and urine exosomes of bladder cancer, circPRMT5 sponges miR-30c through the snail1/E-cadherin pathway to enhance the EMT process, while circ-PDE8A, from hepatic metastatic PDAC cells, acts as a sponge of miR-338 to up-regulate MACC1 and then increases the invasive growth of PDAC cells, thus affecting the tumor progression [120]. Therefore, circRNAs play potentially important roles in the tumor microenvironment through interacting miRNAs, and a circRNA-associated ceRNA network may be a suitable approach to screening a novel biomarker for cancer.…”

Section: Potential Roles Of Circrnas In Tumor Microenvironment Throug...mentioning

confidence: 99%

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

Guo

Jia

Luo

et al. 2022

IJMS

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Circular RNAs (circRNAs), a class of new endogenous non-coding RNAs (ncRNAs), are closely related to the carcinogenic process and play a critical role in tumor metastasis. CircRNAs can lay the foundation for tumor metastasis via promoting tumor angiogenesis, make tumor cells gain the ability of migration and invasion by regulating epithelial-mesenchymal transition (EMT), interact with immune cells, cytokines, chemokines, and other non-cellular components in the tumor microenvironment, damage the normal immune function or escape the immunosuppressive network, and further promote cell survival and metastasis. Herein, based on the characteristics and biological functions of circRNA, we elaborated on the effect of circRNA via circRNA-associated competing endogenous RNA (ceRNA) network by acting as miRNA/isomiR sponges on tumor angiogenesis, cancer cell migration and invasion, and interaction with the tumor microenvironment (TME), then explored the potential interactions across different RNAs, and finally discussed the potential clinical value and application as a promising biomarker. These results provide a theoretical basis for the further application of metastasis-related circRNAs in cancer treatment. In summary, we briefly summarize the diverse roles of a circRNA-associated ceRNA network in cancer metastasis and the potential clinical application, especially the interaction of circRNA and miRNA/isomiR, which may complicate the RNA regulatory network and which will contribute to a novel insight into circRNA in the future.

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“…Several excellent reviews have recently covered a variety of strategies to manipulate the medicinal potential of ncRNAs by using small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), short hairpin RNAs (shRNAs), anti-microRNAs (anti-miRNAs), miRNA mimics, miRNA sponges, therapeutic circular RNAs (cirRNAs), and CRISPR-Cas9based gene editing [6,20,21]. The value of developing therapeutic targeting of ncRNA, while obvious, faces significant obstacles associated with specificity, delivery, and tolerability.…”

Section: Noncoding Rna Therapeutics Approved By Regulatory Agenciesmentioning

confidence: 99%

Noncoding-RNA-Based Therapeutics with an Emphasis on Prostatic Carcinoma—Progress and Challenges

Nava

Perera²,

Kumar

et al. 2022

Vaccines

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Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as “the dark matter of the nucleus”, and unraveling their role in physiologic and pathologic processes will provide vast opportunities for basic and translational research with the potential for significant therapeutic progress. Consequently, strong efforts are underway to exploit the therapeutic utility of ncRNA, some of which have been approved by the US Food and Drug Administration and the European Medicines Agency. The use of ncRNA therapeutics (or “vaccines” if defined as anti-disease agents) may result in improved curative strategies when used alone or in combination with existing treatments. This review will focus on the role of ncRNA therapeutics in prostatic carcinoma while exploring basic biological aspects of these molecules that represent about 97% of the transcriptome in humans.

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Insights into the Evolving Roles of Circular RNAs in Cancer

Cited by 19 publications

References 66 publications

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

Noncoding-RNA-Based Therapeutics with an Emphasis on Prostatic Carcinoma—Progress and Challenges

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