Pseudogenes as Competitive Endogenous RNAs: Testing miRNA Dependency

Author(s):  
Xiaonan Xu ◽  
Florian A. Karreth
2021 ◽  
Vol 11 (3) ◽  
pp. 219
Author(s):  
Ya-Ling Yang ◽  
Yen-Hsiang Chang ◽  
Chia-Jung Li ◽  
Ying-Hsien Huang ◽  
Ming-Chao Tsai ◽  
...  

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lasse S. Kristensen ◽  
Karoline K. Ebbesen ◽  
Martin Sokol ◽  
Theresa Jakobsen ◽  
Ulrik Korsgaard ◽  
...  

Abstract Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellular expression patterns of ciRS-7 in colon cancer and show that ciRS-7 is completely absent in the cancer cells, but highly expressed in stromal cells within the tumor microenvironment. Additionally, our data suggest that this generally apply to classical oncogene-driven adenocarcinomas, but not to other cancers, including malignant melanoma. Moreover, we find that correlations between circRNA and mRNA expression, which are commonly interpreted as evidence of a ceRNA function, can be explained by different cancer-to-stromal cell ratios among the studied tumor specimens. Together, these results have wide implications for future circRNA studies and highlight the importance of spatially resolving expression patterns of circRNAs proposed to function as ceRNAs.


2014 ◽  
Vol 54 (5) ◽  
pp. 711-713 ◽  
Author(s):  
Jennifer A. Broderick ◽  
Phillip D. Zamore

Heliyon ◽  
2020 ◽  
Vol 6 (5) ◽  
pp. e03978 ◽  
Author(s):  
Dengzhong Sun ◽  
Yongzhi Miao ◽  
Wu Xu ◽  
Weijun Shi ◽  
Lili Wang ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Zhang ◽  
Zixiang Liu ◽  
Yingchuang Tang ◽  
Xiaofeng Shao ◽  
Xi Hua ◽  
...  

Chordoma is a relatively rare malignant bone tumor with high local recurrence. To date, the mechanism remains unclear. lncRNAs play a pivotal role in tumorigenesis by acting as competitive endogenous RNAs of microRNAs. However, the biological role of lncRNA is still unclear in chordoma. In this research, our aim is to investigate the roles and regulation mechanisms of lncRNA NONHSAT114552 in chordoma development. The expression level of NONHSAT114552 and miR-320d in chordoma tissues was determined by qRT-PCR. Meantime, the correlation between NONHSAT114552 and clinical prognosis was also studied. Bioinformatics analysis and luciferase reporter assays were used to verify the relationship between NONHSAT114552 and miR-320d, and between miR-320d and Neuropilin 1 (NRP1). In addition, effects of NONHSAT114552 on chordoma cells (U-CH1 and U-CH2) proliferation and invasion and its regulation on miR-320d were also evaluated. Furthermore, the influences of NONHSAT114552/miR-320d/NRP1 axis on chordoma tumorigenesis were investigated in vivo. NONHSAT114552 was overexpressed while miR-320d was down-regulated in chordoma tissue compared to fetal nucleus pulposus. Kaplan-Meier survival analysis showed that NONHSAT114552 overexpression was associated with patients’ poor prognosis. Knockdown of NONHSAT114552 significantly suppressed chordoma cell proliferation and invasion. In vitro studies confirmed that NONHSAT114552 acted as ceRNA to regulate NRP1 by directly sponging miR-320d, thus facilitating chordoma cell proliferation and invasion. In vivo study demonstrated that NONHSAT114552 moderated chordoma growth by sponging miR-320d to regulating NRP1. Our findings indicate that lncRNA NONHSAT114552 exhibits a critical role in the tumorigenesis and development of chordoma and it may become one potential prognostic marker and therapeutic target for this disease. .


2021 ◽  
Author(s):  
Dong-Hui Liu ◽  
Xiu Yang ◽  
Han Meng ◽  
Gui Yun Zhang ◽  
Shanghang Shen

Abstract Glioblastoma (GBM) is the most common and deadly tumor in the central nervous system. Recent studies illuminated that long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) and play an important role in GBM by regulating immune responses. Here, GBM datasets from TCGA database were analyzed to obtain 356 significantly differentially expressed lncRNAs (DE-lncRNAs), 4951 DE-mRNAs, and 34 DE-miRNAs in GBM, respectively. For mRNAs, 369 DE-mRNAs were identified as immune-related genes in Immport database. For DE-lncRNAs, univariate analysis identified 39 DE-lncRNAs with prognostic significance, and 9 DE-lncRNAs are included in ImmLnc database. Then, combined analysis was conducted, by integrating 9 immune related DE-lncRNAs, 369 immune related DE-mRNAs and 34 DE-miRNAs, and generated a ceRNA network composed of 2 upregulated lncRNAs (LINC01268 and CTB-31O20.2), 3 downregulated miRNAs and 5 upregulated mRNAs. Then we focused on LINC01268 and CTB-31O20.2, and Kaplan-Meier survival, univariate and multivariate Cox regression analysis showed that LINC01268 and CTB-31O20.2 serve as independent protective prognostic markers in GBM. Finally, LINC01268 and CTB-31O20.2 overexpression was conducted in GBM cell U251. CCK8, transwell and scratch healing assay indicated that LINC01268 and CTB-31O20.2 inhibits GBM cell line U251 proliferation, invasion and migration. To sum up, LINC01268 and CTB-31O20.2 are independent prognostic immune related markers, and reduces cancer cell proliferation and metastasis in GBM.


2019 ◽  
Author(s):  
Xi Sun ◽  
Hongxiang Zheng ◽  
Jinlu Li ◽  
Na Sui

Abstract LncRNAs can act as competitive endogenous RNAs (ceRNAs) to competitively bind miRNAs, thereby indirectly regulating the transcription levels of other RNA transcripts to confer resistance to plants. But how specific ceRNAs respond to salt stress in sweet sorghum is still unclear. In this study, 126 and 133 differentially expressed lncRNAs were identified in salt-tolerant sweet sorghum (M-81E) and a salt-sensitive line (Roma) by high-throughput RNA-seq, respectively. And five new lncRNAs were identified in M-81E and Roma after salt stress treatment, lncRNA13472, lncRNA11310, lncRNA2846, lncRNA26929 and lncRNA14798 acted as ceRNAs to regulate the expression of target genes related to salt resistance by binding the five miRNAs sbi-MIR169b-p3, sbi-MIR5567-p3-2ss16CT17TC, sbi-MIR5567-p5-2, sbi-MIR5567-p5-2ss17CT18TC and PC-3p-270284-34, respectively. The target genes mainly included proton pump proteins, transport proteinsantioxidants, signal transduction proteins and transcription factors. However M-81E had more complex ceRNAs network than in Roma, which might be related with its different salt tolerance. In summary, this study identified a new ceRNA network within the transcriptome and revealed the effect of lncRNAs in the salt stress response.


2020 ◽  
Author(s):  
Lining Huang ◽  
Xingming Jiang ◽  
Zhenglong Li ◽  
Jinglin Li ◽  
Xuan Lin ◽  
...  

Abstract Background: Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown. Methods: The linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments. Results: Linc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506. Conclusions: The data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.


Author(s):  
Zhenguo Yang ◽  
Tianle He ◽  
Qingyun Chen

The muscle growth and development of livestock animals is a complex, multistage process, which is regulated by many factors, especially the genes related to muscle development. In recent years, it has been reported frequently that circular RNAs (circRNAs) are involved widely in cell proliferation, cell differentiation, and body development (including muscle development). However, the research on circRNAs in muscle growth and development of livestock animals is still in its infancy. In this paper, we briefly introduce the discovery, classification, biogenesis, biological function, and degradation of circRNAs and focus on the molecular mechanism and mode of action of circRNAs as competitive endogenous RNAs in the muscle development of livestock and poultry. In addition, we also discuss the regulatory mechanism of circRNAs on muscle development in livestock in terms of transcription, translation, and mRNAs. The purpose of this article is to discuss the multiple regulatory roles of circRNAs in the process of muscle development in livestock, to provide new ideas for the development of a new co-expression regulation network, and to lay a foundation for enriching livestock breeding and improving livestock economic traits.


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