Decoding competing endogenous RNA networks for cancer biomarker discovery

2019 ◽  
Vol 21 (2) ◽  
pp. 441-457 ◽  
Author(s):  
Xin Qi ◽  
Yuxin Lin ◽  
Jiajia Chen ◽  
Bairong Shen
Keyword(s):  
Cancer Biology ◽  
Biomarker Discovery ◽  
Regulatory System ◽  
Regulatory Function ◽  
Circular Rnas ◽  
Cancer Management ◽  
Cerna Network ◽  
Competing Endogenous Rnas ◽  
Experimental Approaches ◽  
Global Understanding

Abstract Crosstalk between competing endogenous RNAs (ceRNAs) is mediated by shared microRNAs (miRNAs) and plays important roles both in normal physiology and tumorigenesis; thus, it is attractive for systems-level decoding of gene regulation. As ceRNA networks link the function of miRNAs with that of transcripts sharing the same miRNA response elements (MREs), e.g. pseudogenes, competing mRNAs, long non-coding RNAs, and circular RNAs, the perturbation of crucial interactions in ceRNA networks may contribute to carcinogenesis by affecting the balance of cellular regulatory system. Therefore, discovering biomarkers that indicate cancer initiation, development, and/or therapeutic responses via reconstructing and analyzing ceRNA networks is of clinical significance. In this review, the regulatory function of ceRNAs in cancer and crucial determinants of ceRNA crosstalk are firstly discussed to gain a global understanding of ceRNA-mediated carcinogenesis. Then, computational and experimental approaches for ceRNA network reconstruction and ceRNA validation, respectively, are described from a systems biology perspective. We focus on strategies for biomarker identification based on analyzing ceRNA networks and highlight the translational applications of ceRNA biomarkers for cancer management. This article will shed light on the significance of miRNA-mediated ceRNA interactions and provide important clues for discovering ceRNA network-based biomarker in cancer biology, thereby accelerating the pace of precision medicine and healthcare for cancer patients.

scholarly journals Multivariate competing endogenous RNA network characterization for cancer MicroRNA biomarker discovery: a novel bioinformatics model with application to prostate cancer metastasis

2022 ◽  
Author(s):  
Yuxin Lin ◽  
Xin Qi ◽  
Jing Chen ◽  
Bairong Shen
Keyword(s):  
Prostate Cancer ◽  
Cancer Metastasis ◽  
Biomarker Discovery ◽  
Characteristic Curve ◽  
Mapk Signaling ◽  
Competing Endogenous Rna ◽  
Cancer Management ◽  
Cerna Network ◽  
Prostate Cancer Metastasis ◽  
Underlying Mechanisms

Abstract Background MicroRNAs (miRNAs) are post-transcriptional regulators with the potential as biomarkers for cancer management. Data-driven competing endogenous RNA (ceRNA) network modeling is an effective way to decipher the complex interplay between miRNAs and spongers. However, no general rules are discovered for ceRNA network-based biomarker prioritization. Methods and Results In this study, a novel bioinformatics model was developed by integrating gene expression with multivariate miRNA-target data for ceRNA network-based biomarker discovery. Compared with traditional methods, the structural vulnerability in human lncRNA-miRNA-mRNA network was comprehensively analyzed, and the single-line regulatory or competing mode among miRNAs, lncRNAs and mRNAs was characterized and quantified as statistical evidence for miRNA biomarker identification. The application of this model to prostate cancer (PCa) metastasis identified a total of 12 miRNAs as putative biomarkers from metastatic PCa-specific lncRNA-miRNA-mRNA network and nine of them have been previously reported as biomarkers for PCa metastasis. The receiver operating characteristic curve and cell line qRT-PCR experiments demonstrated the power of miR-26b-5p, miR-130a-3p, and miR-363-3p as novel candidates for predicting PCa metastasis. Moreover, PCa-associated pathways such as prostate cancer signaling, ERK/MAPK signaling, and TGF-β signaling were significantly enriched by targets of identified miRNAs, indicating the underlying mechanisms of miRNAs in PCa carcinogenesis. Conclusions A novel ceRNA-based bioinformatics model was proposed and applied to screen candidate miRNA biomarkers for PCa metastasis. Functional validations using human samples and clinical data will be performed for future translational studies on the identified miRNAs.

scholarly journals Accentuating CircRNA-miRNA-Transcription Factors Axis: A Conundrum in Cancer Research

2022 ◽  
Vol 12 ◽  
Author(s):  
Deepti Singh ◽  
Prashant Kesharwani ◽  
Nabil A. Alhakamy ◽  
Hifzur R. Siddique
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
Regulatory Function ◽  
Circular Rnas ◽  
Cancer Management ◽  
Disease Biology ◽  
Scientific World ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Mirna Sponges

Circular RNAs (circRNAs) are the newly uncovered class of non-coding RNAs being cognized as profound regulators of gene expression in developmental and disease biology. These are the covalently closed RNAs synthesized when the pre-mRNA transcripts undergo a back-splicing event. In recent years, circRNAs are gaining special attention in the scientific world and are no longer considered as “splicing noise” but rather structurally stable molecules having multiple biological functions including acting as miRNA sponges, protein decoys/scaffolds, and regulators of transcription and translation. Further, emerging evidence suggests that circRNAs are also differentially expressed in multiple cancers where they play oncogenic roles. In addition, circRNAs in association with miRNAs change the expression patterns of multiple transcription factors (TFs), which play important roles in cancer. Thus, the circRNA-miRNA-TFs axis is implicated in the progression or suppression of various cancer types and plays a role in cell proliferation, invasion, and metastasis. In this review article, we provide an outline of the biogenesis, localization, and functions of circRNAs specifically in cancer. Also, we highlight the regulatory function of the circRNA-miRNA-TFs axis in the progression or suppression of cancer and the targeting of this axis as a potential therapeutic approach for cancer management. We anticipate that our review will contribute to expanding the knowledge of the research community about this recent and rapidly growing field of circRNAs for further thorough investigation which will surely help in the management of deadly disease cancer.

scholarly journals Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis

2021 ◽  
Vol 16 (1) ◽  
pp. 523-536
Author(s):  
Minghao Li ◽  
Jianbin Zhuang ◽  
Di Kang ◽  
Yuzhuo Chen ◽  
Weiliang Song
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Spindle Pole ◽  
Circular Rnas ◽  
Cell Progression ◽  
Crc Management ◽  
Common Malignancy

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

scholarly journals Roles of ncRNAs as ceRNAs in Gastric Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1036
Author(s):  
Junhong Ye ◽  
Jifu Li ◽  
Ping Zhao
Keyword(s):  
Gastric Cancer ◽  
Research Strategy ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Cerna Network ◽  
Degree Of Malignancy ◽  
High Degree ◽  
Competitive Endogenous Rna ◽  
Made In

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.

scholarly journals A circular RNAs dataset landscape reveals potential signatures for the detection and prognosis of early-stage lung adenocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiying Chen ◽  
Jiahui Wei ◽  
Min Li ◽  
Yongjuan Zhao
Keyword(s):  
Functional Analysis ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Interaction Analysis ◽  
Early Stage ◽  
Gene Interaction ◽  
Gene Expression Omnibus ◽  
Circular Rnas ◽  
Cerna Network

Abstract Background This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Methods The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed. Results A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. Conclusion Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.

Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase and evidence for functional interaction with the SNF4 protein

1989 ◽  
Vol 9 (11) ◽  
pp. 5034-5044
Author(s):  
J L Celenza ◽  
M Carlson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Mutational Analysis ◽  
Gene Dosage ◽  
Regulatory System ◽  
Kinase Domain ◽  
Regulatory Function ◽  
Protein Kinase Activity ◽  
Glucose Limitation

The SNF1 gene of Saccharomyces cerevisiae encodes a protein-serine/threonine kinase that is required for derepression of gene expression in response to glucose limitation. We present evidence that the protein kinase activity is essential for SNF1 function: substitution of Arg for Lys in the putative ATP-binding site results in a mutant phenotype. A polyhistidine tract near the N terminus was found to be dispensable. Deletion of the large region C terminal to the kinase domain only partially impaired SNF1 function, causing expression of invertase to be somewhat reduced but still glucose repressible. The function of the SNF4 gene, another component of the regulatory system, was required for maximal in vitro activity of the SNF1 protein kinase. Increased SNF1 gene dosage partially alleviated the requirement for SNF4. C-terminal deletions of SNF1 also reduced dependence on SNF4. Our findings suggest that SNF4 acts as a positive effector of the kinase but does not serve a regulatory function in signaling glucose availability.

Circadian Timekeeping in Anticancer Therapeutics: An Emerging Vista of Chronopharmacology Research

2021 ◽  
Vol 22 ◽  
Author(s):  
Alekhya Puppala ◽  
Sourbh Rankawat ◽  
Sandipan Ray
Keyword(s):  
Drug Metabolism ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Biology ◽  
Anticancer Therapy ◽  
Time Of Day ◽  
Circadian Regulation ◽  
Cancer Management ◽  
Anticancer Therapeutics

Background: Intrinsic rhythms in host and cancer cells play an imperative role in tumorigenesis and anticancer therapy. Circadian medicine in cancer is principally reliant on the control of growth and development of cancer cells or tissues by targeting the molecular clock and implementing time-of-day-based anticancer treatments for therapeutic improvements. In recent years, based on extensive high-throughput studies, we witnessed the arrival of several drugs and drug-like compounds that can modulate circadian timekeeping for therapeutic gain in cancer management. Objective: This perspective article intends to illustrate the current trends in circadian medicine in cancer, focusing on clock-modulating pharmacological compounds and circadian regulation of anticancer drug metabolism and efficacy. Scope and Approach: Considering the critical roles of the circadian clock in metabolism, cell signaling, and apoptosis, chronopharmacology research is exceedingly enlightening for understanding cancer biology and improving anticancer therapeutics. In addition to reviewing the relevant literature, we investigated the rhythmic expression of molecular targets for many anticancer drugs frequently used to treat different cancer types. Key Findings and Conclusion: There are adequate empirical pieces of evidence supporting circadian regulation of drug metabolism, transport, and detoxification. Administration of anticancer drugs at specific dosing times can improve their effectiveness and reduce the toxic effects. Moreover, pharmacological modulators of the circadian clock could be used for targeted anticancer therapeutics such as boosting circadian rhythms in the host can markedly reduce the growth and viability of tumors. All in all, precision chronomedicine can offer multiple advantages over conventional anticancer therapy.

scholarly journals Circ_0000215 Exerts Oncogenic Function in Nasopharyngeal Carcinoma by Targeting miR-512-5p

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinping Chen ◽  
Weihua Xu ◽  
Zhichao Ma ◽  
Juan Zhu ◽  
Junjie Hu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cell Counting ◽  
Regulatory Subunit ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Circular Rnas

Background: Increasing circular RNAs (circRNAs) are reported to participate in cancer progression. Nonetheless, the role of circRNAs in nasopharyngeal carcinoma (NPC) has not been fully clarified. This work is aimed to probe the role of circ_0000215 in NPC.Methods: Circ_0000215 expression in NPC tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, 5-bromo-2′-deoxyuridine (BrdU) assay, scratch healing assay and Transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of NPC cells. RNA immunoprecipitation (RIP), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and miR-512-5p, and between miR-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) 3′UTR. The effects of circ_0000215 on NPC growth and metastasis in vivo were examined with nude mice model. Western blot was applied to detect the regulatory effects of circ_0000215 and miR-512-5p on PIK3R1 expression.Results: Circ_0000215 was overexpressed in NPC tissues and cell lines. The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of NPC cells in vitro and in vivo. Additionally, circ_0000215 could also work as a molecular sponge to repress miR-512-5p expression. PIK3R1 was validated as a target gene of miR-512-5p, and circ_0000215 could increase the expression level of PIK3R1 in NPC cells via suppressing miR-512-5p.Conclusion: Circ_0000215 is overexpressed in NPC and exerts oncogenic effects in NPC through regulating miR-512-5p/PIK3R1 axis.

scholarly journals CircRNA Expression Profile during Yak Adipocyte Differentiation and Screen Potential circRNAs for Adipocyte Differentiation

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 414 ◽  
Author(s):  
Yongfeng Zhang ◽  
Xian Guo ◽  
Jie Pei ◽  
Min Chu ◽  
Xuezhi Ding ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Adipocyte Differentiation ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Regulatory Function ◽  
Circular Rnas ◽  
Functional Involvement ◽  
Winter Grazing ◽  
Human And Mouse

The yak (Bos grunniens) is subjected to nutritional deficiency during the whole winter grazing season; deciphering the adipose metabolism and energy homeostasis under cold and nutrients stress conditions could be a novel way to understand the specific mechanism of energy metabolism. Circular RNAs (circRNAs) have elucidated that they play a key role in many biological events, but the regulatory function of adipose development remains mostly unknown. Therefore, the expression pattern of circRNAs were identified for the first time during yak adipocyte differentiation to gain insight into their potential functional involvement in bovine adipogenesis. We detected 7203 circRNA candidates, most of them contained at least two exons, and multiple circRNA isoforms could be generated from one parental gene. Analysis of differential expression circRNAs displayed that 136 circRNAs were differentially expressed at day 12 (Ad) after adipocyte differentiation, compared with the control at day 0 (Pread 0), while 7 circRNAs were detected on day 2. Sanger sequencing validated that six circRNAs had head-to-tail junction, and quantitative real-time PCR (qPCR) results revealed that the expression patterns of ten circRNAs were consistent with their expression levels from RNA-sequencing (RNA-seq) data. We further predicted the networks of circRNA-miRNA-gene based on miRNAs sponging by circRNAs, in which genes were participated in the adipocyte differentiation-related signaling pathways. After that, we constructed several adipocyte differentiation-related ceRNAs and revealed six circRNAs (novel_circ_0009127, novel_circ_0000628, novel_circ_0011513, novel_circ_0010775, novel_circ_0006981 and novel_circ_0001494) were related to adipogenesis. Furthermore, we analyzed the homology among yak, human and mouse circRNAs and found that 3536 yak circRNAs were homologous to human and mouse circRNAs. In conclusion, these findings provide a solid basis for the investigation of yak adipocyte differentiation-related circRNAs and serve as a great reference to study the energy metabolism of high-altitude animals.

scholarly journals Development of an immunogenomic landscape for the competing endogenous RNAs network of peri-implantitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Li ◽  
Jina Zheng ◽  
Chanjuan Gong ◽  
Kengfu Lan ◽  
Yuqing Shen ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Profile Data ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Cerna Network ◽  
Inflammatory Damage ◽  
Competing Endogenous Rnas ◽  
Immune Related Genes ◽  
Important Significance

Abstract Background Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631. Methods In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis. Results In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003). Conclusions Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

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