scholarly journals WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs

2021 ◽  
Vol Volume 14 ◽  
pp. 8737-8751
Author(s):  
Mengxiong Li ◽  
Zhi Zeng ◽  
Aiqing Zhang ◽  
Qingjian Ye ◽  
Shujun Su ◽  
...  
2021 ◽  
Vol 22 (14) ◽  
pp. 7477
Author(s):  
Rok Razpotnik ◽  
Petra Nassib ◽  
Tanja Kunej ◽  
Damjana Rozman ◽  
Tadeja Režen

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.


2021 ◽  
Vol 12 (17) ◽  
pp. 5206-5219
Author(s):  
Meng-Ping Jiang ◽  
Wen-Xiu Xu ◽  
Jun-Chen Hou ◽  
Qi Xu ◽  
Dan-Dan Wang ◽  
...  

2019 ◽  
Vol 20 (16) ◽  
pp. 3926 ◽  
Author(s):  
Xing Zhao ◽  
Yujie Cai ◽  
Jianzhen Xu

CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. In this review, we will first provide an introduction of circRNAs biogenesis, especially the regulation of circRNA by RNA-binding proteins, then we will focus on the recent findings of circRNA molecular mechanisms and functions in cancer development. Finally, some open questions are also discussed.


2019 ◽  
Vol 97 (5) ◽  
pp. 554-562 ◽  
Author(s):  
Xueqin Sun ◽  
Shan Su ◽  
Guoxiang Zhang ◽  
Hong Zhang ◽  
Xiaohui Yu

MicroRNA (miR)-204 is known to be associated with several different diseases. Polycystic ovary syndrome (PCOS) has the highest incidence rate among the endocrine disorders in females between the ages of 18 and 44. We aimed to illustrate the miR-204 function in PCOS. MiR-204 expression levels in tissue and cell were examined through RT-qPCR. Colony formation assay and MTT assay were applied to detect the cell viability. Flow cytometry was employed to examine the apoptosis and cell cycle in cells. RNA binding protein immunoprecipitation assay and luciferase reporter assay were provided to demonstrate the direct interaction between translationally controlled tumor protein (TPT1) and miR-204. The expression of miR-204 was declined in KGN cells and ovarian cortex tissues of PCOS patients. MiR-204 enhanced the colony formation capacity and cell proliferation in KGN cells. Cell cycle and apoptosis were also influenced by miR-204. Since miR-204 has direct interaction with TPT1, TPT1 overexpression suppressed the miR-204-induced apoptosis and cell cycle alteration in KGN cells. MiR-204 inhibits the cell viability and induces apoptosis and cell cycle arrest by directly interacting with TPT1, indicating a role of miR-204 to be a potential target in the PCOS patients.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhengfeng Wang ◽  
Xiujuan Lei

Abstract Background Circular RNAs (circRNAs) are widely expressed in cells and tissues and are involved in biological processes and human diseases. Recent studies have demonstrated that circRNAs can interact with RNA-binding proteins (RBPs), which is considered an important aspect for investigating the function of circRNAs. Results In this study, we design a slight variant of the capsule network, called circRB, to identify the sequence specificities of circRNAs binding to RBPs. In this model, the sequence features of circRNAs are extracted by convolution operations, and then, two dynamic routing algorithms in a capsule network are employed to discriminate between different binding sites by analysing the convolution features of binding sites. The experimental results show that the circRB method outperforms the existing computational methods. Afterwards, the trained models are applied to detect the sequence motifs on the seven circRNA-RBP bound sequence datasets and matched to known human RNA motifs. Some motifs on circular RNAs overlap with those on linear RNAs. Finally, we also predict binding sites on the reported full-length sequences of circRNAs interacting with RBPs, attempting to assist current studies. We hope that our model will contribute to better understanding the mechanisms of the interactions between RBPs and circRNAs. Conclusion In view of the poor studies about the sequence specificities of circRNA-binding proteins, we designed a classification framework called circRB based on the capsule network. The results show that the circRB method is an effective method, and it achieves higher prediction accuracy than other methods.


2019 ◽  
Vol 29 ◽  
pp. S720-S721 ◽  
Author(s):  
Jason Weick ◽  
Brian Rodriguez ◽  
Stephen Amoah ◽  
Michela DellOrco ◽  
Alexander Hafez ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yongqian Chen ◽  
Jintian Miao ◽  
Ge Lou

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine disease that increases the risk of infertility. Circular RNAs (circRNAs) play important roles in regulating the biological processes of PCOS. Our study was designed to explore the function of circ-FURIN in PCOS. Methods Circ-FURIN expression was detected using RT-qPCR. The protein expression of AVEN, BCL2, XIAP and AREL1 was measured using western blot. Dual-luciferase reporter and RNA pull-down assays were applied to clarify the interaction between miR-195-5p and circ-FURIN or BCL2. Functionally, cell proliferation was assessed by MTT and colony formation assays. Cell apoptosis was analyzed by flow cytometry. Results Circ-FURIN was upregulated in PCOS patients and granular cells (GCs). Knockdown of circ-FURIN inhibited cell proliferation and promoted apoptosis of KGN cells, along with the increased expression of caspase-3 and Bax and the decreased levels of p-PI3K. Gene ontology (GO) analysis indicated circ-FURIN is associated with apoptotic signaling pathway and cell death. Subsequently, BCL2 expression was elevated in patients with PCOS and positively regulated by circ-FURIN. Furthermore, circ-FURIN was served as a sponge of miR-195-5p to directly target to BCL2. The levels of miR-195-5p were reduced in PCOS and KGN cells. Knockdown of circ-FURIN decreased the expression of BCL2, which was abolished by miR-195-5p inhibitor. At last, rescue experiments revealed that overexpression of BCL2 reversed the effects of circ-FURIN knockdown on cell proliferation and apoptosis of KGN cells. Conclusions Loss of circ-FURIN alleviated the development of PCOS via miR-195-5p/BCL2 axis. Circ-FURIN may be the novel biomarker for PCOS.


2017 ◽  
Author(s):  
Bin Li ◽  
Xiao-Qin Zhang ◽  
Shu-Rong Liu ◽  
Shun Liu ◽  
Wen-Ju Sun ◽  
...  

AbstractAlthough tens of thousands of circular RNAs (circRNAs) have been identified in mammalian genomes, only few of them have been characterized with biological functions. Here, we report a new approach, circScan, to identify regulatory interactions between circRNAs and RNA-binding proteins (RBPs) by discovering back-splicing reads from Cross-Linking and Immunoprecipitation followed by high-throughput sequencing (CLIP-seq) data. By using our method, we have systematically scanned ~1500 CLIP-seq datasets, and identified ~12540 and ~1090 novel circRNA-RBP interactions in human and mouse genomes, respectively, which include all known interactions between circRNAs and Argonaute (AGO) proteins. More than twenty novel interactions were further experimentally confirmed by RNA Immunoprecipitation quantitative PCR (RIP-qPCR). Importantly, we uncovered that some natural circRNAs interacted with cap-independent translation factors eukaryotic initiation factor 3 (eIF3) and N6-Methyladenosine (m6A), indicating they can be translated into proteins. These findings demonstrate that circRNAs are regulated by various RBPs, suggesting they may play important roles in diverse biological processes.


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