Circular RNAs: Regulators of Cancer-Related Signaling Pathways and Potential Diagnostic Biomarkers for Human Cancers

Yang, Zuozhang; Xie, Lin; Han, Lei; Qu, Xin; Yang, Yihao; Ya, Zhang; He, Zewei; Wang, Yu; Li, Jing

doi:10.7150/thno.19016

Cited by 124 publications

(105 citation statements)

References 136 publications

(125 reference statements)

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“…CircRNA is transcribed by RNA polymerase II without 5'-3' polarity or polyadenine tails. It has the same transcriptional efficiency as linear RNA [53][54][55]. CircRNA is hundreds to thousands of bases long and mainly consists of exons.…”

Section: Introductionmentioning

confidence: 99%

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

et al. 2020

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Non-coding RNAs do not encode proteins and regulate various oncological processes. They are also important potential cancer diagnostic and prognostic biomarkers. Bioinformatics and translation omics have begun to elucidate the roles and modes of action of the functional peptides encoded by ncRNA. Here, recent advances in long non-coding RNA (lncRNA) and circular RNA (circRNA)-encoded small peptides are compiled and synthesized. We introduce both the computational and analytical methods used to forecast prospective ncRNAs encoding oncologically functional oligopeptides. We also present numerous specific lncRNA and circRNA-encoded proteins and their cancer-promoting or cancer-inhibiting molecular mechanisms. This information may expedite the discovery, development, and optimization of novel and efficacious cancer diagnostic, therapeutic, and prognostic protein-based tools derived from non-coding RNAs. The role of ncRNA-encoding functional peptides has promising application perspectives and potential challenges in cancer research. The aim of this review is to provide a theoretical basis and relevant references, which may promote the discovery of more functional peptides encoded by ncRNAs, and further develop novel anticancer therapeutic targets, as well as diagnostic and prognostic cancer markers.

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Section: Introductionmentioning

confidence: 99%

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

et al. 2020

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“…This class includes microRNAs (miRNAs/miRs) and circular RNAs (circRNAs), among others (5). miRNAs have been demonstrated to be major post-transcriptional regulators of gene expression (6) and serve critical functions in vascular biology (7). circRNAs interact with other molecules or miRNAs to regulate gene expression at the post-transcriptional or transcriptional levels (8), thus modulating various biological processes such as cell proliferation, apoptosis, invasion and migration (9).…”

Section: Introductionmentioning

confidence: 99%

CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

2020

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Abdominal aortic aneurysm (AAA) is characterized as dilation of the aortic wall. Dysregulation of vascular smooth muscle cells (VSMCs) can contribute to the development of this phenotype. Circular RNAs and microRNAs (miRNAs) can regulate the proliferation and apoptosis of VSMCs. This present study aimed to identify the mechanisms of action behind the regulation of cerebellar degeneration-related protein 1 antisense RNA (CDR1as)/miRNA (miR)-7 in VSMCs. The expression levels of miR-7 were upregulated, whereas the levels of CDR1as and cytoskeleton-associated protein 4 (CKAP4) were downregulated in aortic specimens obtained from 10 patients who underwent surgery for AAA compared with aortic specimens from 10 control patients who underwent coronary artery bypass surgery. The molecular mechanism of action of CDR1as/miR-7 was investigated in primary VSMCs. The results of Cell Counting kit-8 and cell growth curve assays revealed that overexpression of CDR1as and knockdown of miR-7, increased VSMC proliferation, whereas knockdown of CDR1as and overexpression of miR-7 suppressed VSMC proliferation. In addition, overexpression of CDR1as and knockdown of miR-7, suppressed apoptosis in VSMCs, indicated by the decreased levels of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) activity, whereas knockdown of CDR1as and overexpression of miR-7 exhibited the opposite effects. The results of luciferase reporter and biotin pull-down assays confirmed that CDR1as directly bound to miR-7 and suppressed its expression. Additionally, the CDR1as-induced proliferation and suppressed apoptosis was reversed by the overexpression of miR-7. Furthermore, luciferase reporter, reverse transcription-quantitative PCR and western blot assays revealed that miR-7 directly targeted CKAP4 and suppressed its expression. Additionally, the miR-7-suppressed proliferation and increased ROS and LDH activity were reversed by the overexpression of CKAP4. CDR1as also decreased caspase 3/7 activity, which was reversed by miR-7 mimics. miR-7 increased the activity of caspase 3/7, which was again reversed by the overexpression of CKAP4. Therefore, CDR1as, miR-7 and CKAP4 may act in the same pathway to regulate VSMC proliferation and apoptosis.

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“…Regarding high stability and tissue specificity of circRNAs, they are taken as promising novel biomarkers in numerous diseases [21]. To further identify whether circ-PRKCI can serve as a biomarker in HSCR, the receiver operating characteristic (ROC) curves analysis was then evaluated.…”

Section: Characteristics and Expression Of Circ-prkci In Hscrmentioning

confidence: 99%

Down-regulation of circ-PRKCI inhibits cell migration and proliferation in Hirschsprung disease by suppressing the expression of miR-1324 target PLCB1

et al. 2018

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Circular RNAs (circRNAs) are a novel class of noncoding RNAs (ncRNAs), which have been shown to participate in intracellular RNA regulatory networks and play vital roles in many pathological processes. Recently, circular RNA_PRKCI (circ-PRKCI) has been reported to regulate cell proliferation, migration and invasion in several human cancers. Hirschsprung disease (HSCR) is a well-known congenital gut motility disorder which roots in the aberrance of cranial-caudal neural crest cell migration. In this study, we investigated whether circ-PRKCI may affect cell migration and proliferation in HSCR. Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression of circ-PRKCI in 48 HSCR aganglionic tissues and 48 normal bowel tissues. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay verified the direct interaction between miR-1324 and PLCB1 or circ-PRKCI. Cell counting Kit-8 (CCK-8) and Ethynyldeoxyuridine (EdU) assays were employed to appraise the effects of miR-1324 or circ-PRKCI on cell proliferative potential, while transwell was performed to detect the migration in vitro. We found that circ-PRKCI was significantly down-regulated in HSCR aganglionic tissues. Morever, knockdown of circ-PRKCI suppressed cell proliferation and migration in vitro. Mechanistically, we confirmed that circ-PRKCI functioned as a molecular sponge for miR-1324 to upregulate the expression of PLCB1. In conclusion, our present study revealed the important role of circ-PRKCI-miR-1324-PLCB1 regulatory network in HSCR, providing a novel insight for the pathogenesis of HSCR.

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Circular RNAs: Regulators of Cancer-Related Signaling Pathways and Potential Diagnostic Biomarkers for Human Cancers

Cited by 124 publications

References 136 publications

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

Down-regulation of circ-PRKCI inhibits cell migration and proliferation in Hirschsprung disease by suppressing the expression of miR-1324 target PLCB1

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