Circular RNA-ITCH Suppresses Lung Cancer Proliferation via Inhibiting the Wnt/<i>β</i>-Catenin Pathway

Wan, Li; Zhang, Lin; Fan, Kai; Cheng, Zaixing; Sun, Quanchao; Wang, Jianjun

doi:10.1155/2016/1579490

Cited by 292 publications

(275 citation statements)

References 55 publications

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“…14,15 The miR-223 is known to cause cardiac hypertrophy and the heart-related circRNA HRCR is thought to protect the heart by sponging miR-223. 49 The circRNA TTBK2 was shown to promote malignancy of gliomas by modulating miR-217 that controls hepatocyte nuclear factor 1β/Derlin-1 pathway, 50 and circRNA ITCH is known to suppress lung cancer by sponging miR-7 and miR-214 thereby suppressing the activation of Wnt/β-catenin 51 . In the present study, the circRNAs altered after stroke were identified to contain binding sites for many miRNAs indicating their potential to modulate miRNA-mediated translation and thus ischemic pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia

Mehta

Pandi

Vemuganti

2017

Stroke

142

105

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Background and Purpose Circular RNAs (circRNAs) are a novel class of non-coding RNAs formed from many protein-coding genes by backsplicing. Although their physiologic functions are not yet completely defined, they are thought to control transcription, translation and miRNA levels. We investigated whether stroke changes the circRNAs expression profile in the mouse brain. Methods Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO), and circRNA expression profile was evaluated in the penumbral cortex at 6h, 12h, and 24h of reperfusion using circRNA microarrays and real-time PCR. Bioinformatics analysis was conducted to identify miRNA binding sites, transcription factor binding and gene ontology of circRNAs altered after ischemia. Results 1,320 circRNAs were expressed at detectable levels mostly from exonic (1,064) regions of the genes in the cerebral cortex of sham animals. Of those, 283 were altered (>2-fold) at least at one of the reperfusion time points, whereas 16 were altered at all 3-time points of reperfusion after transient MCAO studied compared to sham. Post-ischemic changes in circRNAs identified by microarray analysis were confirmed by real-time PCR. Bioinformatics showed that these 16 circRNAs contain binding sites for many miRNAs. Promoter analysis showed that the circRNAs altered after stroke might be controlled by a set of transcription factors. The major biological and molecular functions controlled by circRNAs altered after transient MCAO are biological regulation, metabolic process, cell communication, and binding to proteins, ions and nucleic acids. Conclusions This is a first study that shows that stroke alters the expression of circRNAs with possible functional implication to post-stroke pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia

Mehta

Pandi

Vemuganti

2017

Stroke

142

105

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“…As reported in NSCLC, circ-ITCH functions as a “sponge” to block miR-7 or miR-214 and assures the stable expression of the ubiquitin E3 ligase ITCH to inhibit the Wnt/β-catenin signaling pathway, which can indirectly inhibit the proliferation of lung cancer cells through promoting the ubiquitination and degradation of Dvl2 [33]. In addition to being a microRNA “sponge” or regulator of gene transcription [34], circRNAs not only can produce pseudogenes to alter the genomic DNA composition [18, 20, 35] but also possess a protein translation function [19].…”

Section: Discussionmentioning

confidence: 99%

“…Given that circRNAs could function as miRNA sponges [33] and most of the circRNAs contain one or more miRNAs binding sites, the dysregulated circRNAs in NSCLC were likely due to an involvement in miRNA blockage, thereby contributing to the development of disease. The circRNA/miRNA interaction predicted that hsa_circRNA_404833 is potentially able to interact with miR-149-5p, which reduces cell motility and is involved in the acquired gefitinib resistance in lung adenocarcinoma [39].…”

Section: Discussionmentioning

confidence: 99%

CircRNA Expression Profile in Early-Stage Lung Adenocarcinoma Patients

Zhao

Wang

et al. 2017

Cell Physiol Biochem

106

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Background/Aims: Lung adenocarcinoma, a form of non-small cell lung cancer with high lethality at an advanced stage, is becoming more common in women, non- or never-smokers, and even young adults. At present, there are still no effective early diagnosis methods for patients to be cured in a timely manner. Circular RNAs (circRNAs), which are stable and conserved non-coding RNA in mammalian cells, have been reported to be widely involved in the processes of cancer disease. However, it is still a puzzle as to which specific circRNAs are involved in the development of early-stage lung adenocarcinoma. Methods: Tumor samples and paired adjacent normal tissues from 4 patients with early-stage lung adenocarcinoma were selected to investigate the expression profile of circRNAs by using a high-throughput circRNA microarray. Bioinformatic analyses were conducted to screen those differentially expressed circRNAs. qRT-PCR and sequencing were performed to assure the microarray data. Results: A total of 357 circRNAs were dysregulated in the tumor samples, which suggests potential roles in lung cancer. qRT-PCR detection showed that five selected circRNAs were identical to the microarray data, and the potential circRNA-miRNA interactions were predicted. Conclusion: This work illustrates that clusters of circRNAs are aberrantly expressed in early-stage lung adenocarcinoma, which might offer potential targets for the early diagnosis of this disease and new genetic insights into lung cancer.

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“…These investigations have shown that circRNAs are frequently downregulated in several types of cancer (e.g., colorectal cancer, ovarian cancer, and gastric cancer) [64–66]. Just few of these studies attempted to functionally explain how abnormal expression of circRNAs could impair physiological cell homeostasis and thus promote cancer phenotypes [67–69]. …”

Section: Introductionmentioning

confidence: 99%

Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer

Ragusa

Barbagallo

Brex

et al. 2017

International Journal of Genomics

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Over the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression. ncRNAs can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of RNAs (e.g., mRNAs, miRNAs, lncRNAs, and circRNAs). Such a hidden network of RNA-RNA competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncRNAs as keystones of network structural integrity makes them very attractive and promising targets for innovative RNA-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncRNAs, with a special focus on cancer; and (2) the main issues and criticisms concerning ncRNAs targeting in therapeutics.

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Circular RNA-ITCH Suppresses Lung Cancer Proliferation via Inhibiting the Wnt/β-Catenin Pathway

Cited by 292 publications

References 55 publications

Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia

Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia

CircRNA Expression Profile in Early-Stage Lung Adenocarcinoma Patients

Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer

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