Research progress of competing endogenous RNA_Journal of Biomedical Engineering

Authors：

WANG Lin ¹ ,  LIU Jie ²

1. The 2nd clinical college of China Medical University, Shenyang 110013, P.R.China;
2. The Science Experiment Center of China Medical University, Shenyang 110122, P.R.China;

Corresponding author：

Keywords：

competing endogenous RNA; microRNAs; microRNA response element; posttranscriptional regulation

DOI：

10.7507/1001-5515.201606080

Video：

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Abstract Full text Figures/Tables Video References Cited by

The competing endogenous RNA (ceRNA) hypothesis is a new pattern of gene posttranscriptional regulation. Encoding mRNA, long noncoding RNA (lncRNA), pseudogene transcript, circular RNA (circRNA), etc. can regulate gene expression by binding microRNA (miRNA). According to the research, ceRNA regulatory network participates in the maintenance of normal physiological state, occurrence and development of diseases. This paper reviewed ceRNA with the following respects: the proposal of ceRNA hypothesis, members of ceRNA regulatory network, research status, limitations and future development directions of this hypothesis. It will contribute to clarify the pathogenesis of much diseases including tumor and provide a new strategy for the diagnosis and treatment of disease.

Citation： WANG Lin, LIU Jie. Research progress of competing endogenous RNA. Journal of Biomedical Engineering, 2017, 34(6): 967-971. doi: 10.7507/1001-5515.201606080 Copy

1.	Martirosyan A, De Martino A, Pagnani A A, et al. ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins. Sci Rep, 2017, 7: 43673.
2.	Sanchez-Taltavull D, Macleod M, Perkins T J. On cross-conditional and fluctuation correlations in competitive RNA networks. Bioinformatics, 2016, 32(17): 790-797.
3.	Seitz H. Redefining microRNA targets. Curr Biol, 2009, 19(10): 870-873.
4.	Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell, 2011, 146(3): 353-358.
5.	Li Chengyun, Liang Geyu, Yao Wenzhuo, et al. Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer. Int J Oncol, 2016, 48(5): 1965-1976.
6.	Li Mingxun, Sun Xiaomei, Cai Hanfang, et al. Long non-coding RNA ADNCR suppresses adipogenic differentiation by targeting miR-204. Biochim Biophys Acta, 2016, 1859(7): 871-882.
7.	Yang J, Li T, Gao C, et al. Foxo1 3’-UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett, 2014, 588: 3218-3224.
8.	Liu Kunmei, Guo Le, Guo Yongjian, et al. AEG-1 3’-untranslated region functions as a ceRNA in inducing epithelial-mesenchymal transition of human non-small cell lung cancer by regulating miR-30a activity. Eur J Cell Biol, 2015, 94(1): 22-31.
9.	Zhang Jie, Liu Huan, Lin Heng, et al. Sp1 is a competitive endogenous RNA of Klf4 during odontoblast differentiation. International Journal of Biochemistry & Cell Biology, 2017, 85: 159-165.
10.	Evans J R, Feng F Y, Chinnaiyan A M. The bright side of dark matter:lncRNAs in cancer, J Clin Invest, 2016, 126(8): 2775-2782.
11.	Yang Chao, Wu Di, Gao Lin, et al. Competing endogenous RNA networks in human cancer: hypothesis, validation, and perspectives. Oncotarget, 2016, 7(12): 13479-13490.
12.	Cai Yifei, Sun Ziling, Jia Huizhen, et al. Rpph1 upregulates CDC42 expression and promotes hippocampal neuron dendritic spine formation by competing with miR-330-5p. Front Mol Neurosci, 2017, 10: 27.
13.	Lin Zongwei, Ge Junfeng, Wang Zhe, et al. Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk. Sci Rep, 2017, 7: 42498.
14.	Zhang C Z. Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Gene, 2017, 607: 47-55.
15.	Zhu Shaoping, Wang Junyu, Wang Xianguo, et al. Long intergenic non-protein coding RNA 00858 functions as a competing endogenous RNA for miR-422a to facilitate the cell growth in non-small cell lung cancer. Aging (Albany NY), 2017, 9(2): 475-486.
16.	Qu Le, Ding Jin, Chen Cheng, et al. Exosome-Transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell, 2016, 29(5): 653-668.
17.	Shi Xuefei, Nie Fengqi, Wang Zhaoxia, et al. Pseudogene-expressed RNAs: a new frontier in cancers. Tumour Biol, 2016, 37(2): 1471-1478.
18.	An Y, Furber K L, Ji S. Pseudogenes regulate parental gene expression via ceRNA network, J Cell Mol Med, 2017, 21(1): 185-192.
19.	Wang Lei, Zhang Ning, Wang Zun, et al. Pseudogene PTENP1 functions as a competing endogenous RNA (ceRNA) to regulate PTEN expression by sponging miR-499-5p. Biochemistry (Mosc), 2016, 81(7): 739-747.
20.	Tay Y, Rinn J, Pandolfi P P. The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014, 505(7483): 344-352.
21.	Migault M, Donnou F E, Galibert M D, et al. Definition and identification of small RNA sponges: Focus on miRNA sequestration, Methods, 2017, 117: 35-47.
22.	Thomson D W, Dinger M E. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet, 2016, 17(5): 272-283.
23.	Barrett S P, Salzman J. Circular RNAs: analysis,expression and potential functions. Development, 2016, 143(11): 1838-1847.
24.	Kulcheski F R, Christoff A P, Margis R. Circular RNAs are miRNA sponges and can be used as a new class of biomarker, J Biotechnol, 2016, 238: 42-51.
25.	Liu J, Liu T, Wang X, et al. Circles reshaping the RNA world: from waste to treasure, Mol Cancer, 2017, 16(1): 58.
26.	Peng Lei, Chen Guanglin, Zhu Zhongxian, et al. Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung’s disease. Oncotarget, 2017, 8(1): 808-818.
27.	Zhong Zhenyu, Lv Mengxin, Chen Junxia. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep, 2016, 6: 30919.
28.	He J, Xie Q, Xu H, et al. Circular RNAs and cancer, Cancer Lett, 2017, 396: 138-144.
29.	Lu D, Xu A D. Mini review: circular RNAs as potential clinical biomarkers for disorders in the central nervous system, Front Genet, 2016, 7:53.
30.	Kumari B, Jain P, Das S, et al. Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells. Sci Rep, 2016, 6: 20263.
31.	Nunes A C. Viral pathogenesis: HCV RNA acts as a miR-122 sponge. Nature Reviews Microbiology, 2015, 13(5): 250.
32.	Zhu Mu, Liu Jiafan, Xiao Jia, et al. Lnc-mg is a long non-coding RNA that promotes myogenesis. Nat Commun, 2017, 8: 14718.
33.	Pratt T, Price D J. Junk DNA used in cerebral cortical evolution. Neuron, 2016, 90(6): 1141-1143.
34.	Su Zhaoran, Zhi Xiaofei, Zhang Qun, et al. LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier. FEBS Lett, 2016, 590(9): 1354-1364.
35.	Liu Qiang, Zhang Xin, Hu Xiaoqing, et al. Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 ‘sponge’ in human cartilage degradation. Sci Rep, 2016, 6: 22572.
36.	Shen S, Jiang H, Bei Y, et al. Long non-coding RNAs in cardiac remodeling, Cell Physiol Biochem, 2017, 41(5): 1830-1837.
37.	Wang Kun, Long Bo, Zhou Luyu, et al. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun, 2014, 5: 3596.
38.	Wang Kun, Long Bo, Liu Fang, et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J, 2016, 37(33): 2602-2611.
39.	Liu X H, Sun M, Nie F Q, et al. Lnc RNA HOTAIR funclions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer, 2014, 13: 92.
40.	Tang J, Zhuo H, Zhang X, et al. A novel biomarker Linc00974 interacting with KRTl9 promotes proliferation and metastasis in hepatocellular carcinoma. Cell Death & Disease, 2014, 5: e1549.
41.	Conte F, Fiscon G, Chiara M, et al. Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer. PLoS One, 2017, 12(2): e0171661.
42.	Zhang Shilong, Dong Xinxin, Ji Tongyu, et al. Long non-coding RNA UCA1 promotes cell progression by acting as a competing endogenous RNA of ATF2 in prostate cancer. Am J Transl Res, 2017, 9(2): 366-375.
43.	Chiu Y C, Wang Liju, Lu T P, et al. Differential correlation analysis of glioblastoma reveals immune ceRNA interactions predictive of patient survival. BMC Bioinformatics, 2017, 18(1): 132.

1. Martirosyan A, De Martino A, Pagnani A A, et al. ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins. Sci Rep, 2017, 7: 43673.
2. Sanchez-Taltavull D, Macleod M, Perkins T J. On cross-conditional and fluctuation correlations in competitive RNA networks. Bioinformatics, 2016, 32(17): 790-797.
3. Seitz H. Redefining microRNA targets. Curr Biol, 2009, 19(10): 870-873.
4. Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell, 2011, 146(3): 353-358.
5. Li Chengyun, Liang Geyu, Yao Wenzhuo, et al. Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer. Int J Oncol, 2016, 48(5): 1965-1976.
6. Li Mingxun, Sun Xiaomei, Cai Hanfang, et al. Long non-coding RNA ADNCR suppresses adipogenic differentiation by targeting miR-204. Biochim Biophys Acta, 2016, 1859(7): 871-882.
7. Yang J, Li T, Gao C, et al. Foxo1 3’-UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett, 2014, 588: 3218-3224.
8. Liu Kunmei, Guo Le, Guo Yongjian, et al. AEG-1 3’-untranslated region functions as a ceRNA in inducing epithelial-mesenchymal transition of human non-small cell lung cancer by regulating miR-30a activity. Eur J Cell Biol, 2015, 94(1): 22-31.
9. Zhang Jie, Liu Huan, Lin Heng, et al. Sp1 is a competitive endogenous RNA of Klf4 during odontoblast differentiation. International Journal of Biochemistry & Cell Biology, 2017, 85: 159-165.
10. Evans J R, Feng F Y, Chinnaiyan A M. The bright side of dark matter:lncRNAs in cancer, J Clin Invest, 2016, 126(8): 2775-2782.
11. Yang Chao, Wu Di, Gao Lin, et al. Competing endogenous RNA networks in human cancer: hypothesis, validation, and perspectives. Oncotarget, 2016, 7(12): 13479-13490.
12. Cai Yifei, Sun Ziling, Jia Huizhen, et al. Rpph1 upregulates CDC42 expression and promotes hippocampal neuron dendritic spine formation by competing with miR-330-5p. Front Mol Neurosci, 2017, 10: 27.
13. Lin Zongwei, Ge Junfeng, Wang Zhe, et al. Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk. Sci Rep, 2017, 7: 42498.
14. Zhang C Z. Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Gene, 2017, 607: 47-55.
15. Zhu Shaoping, Wang Junyu, Wang Xianguo, et al. Long intergenic non-protein coding RNA 00858 functions as a competing endogenous RNA for miR-422a to facilitate the cell growth in non-small cell lung cancer. Aging (Albany NY), 2017, 9(2): 475-486.
16. Qu Le, Ding Jin, Chen Cheng, et al. Exosome-Transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell, 2016, 29(5): 653-668.
17. Shi Xuefei, Nie Fengqi, Wang Zhaoxia, et al. Pseudogene-expressed RNAs: a new frontier in cancers. Tumour Biol, 2016, 37(2): 1471-1478.
18. An Y, Furber K L, Ji S. Pseudogenes regulate parental gene expression via ceRNA network, J Cell Mol Med, 2017, 21(1): 185-192.
19. Wang Lei, Zhang Ning, Wang Zun, et al. Pseudogene PTENP1 functions as a competing endogenous RNA (ceRNA) to regulate PTEN expression by sponging miR-499-5p. Biochemistry (Mosc), 2016, 81(7): 739-747.
20. Tay Y, Rinn J, Pandolfi P P. The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014, 505(7483): 344-352.
21. Migault M, Donnou F E, Galibert M D, et al. Definition and identification of small RNA sponges: Focus on miRNA sequestration, Methods, 2017, 117: 35-47.
22. Thomson D W, Dinger M E. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet, 2016, 17(5): 272-283.
23. Barrett S P, Salzman J. Circular RNAs: analysis,expression and potential functions. Development, 2016, 143(11): 1838-1847.
24. Kulcheski F R, Christoff A P, Margis R. Circular RNAs are miRNA sponges and can be used as a new class of biomarker, J Biotechnol, 2016, 238: 42-51.
25. Liu J, Liu T, Wang X, et al. Circles reshaping the RNA world: from waste to treasure, Mol Cancer, 2017, 16(1): 58.
26. Peng Lei, Chen Guanglin, Zhu Zhongxian, et al. Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung’s disease. Oncotarget, 2017, 8(1): 808-818.
27. Zhong Zhenyu, Lv Mengxin, Chen Junxia. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep, 2016, 6: 30919.
28. He J, Xie Q, Xu H, et al. Circular RNAs and cancer, Cancer Lett, 2017, 396: 138-144.
29. Lu D, Xu A D. Mini review: circular RNAs as potential clinical biomarkers for disorders in the central nervous system, Front Genet, 2016, 7:53.
30. Kumari B, Jain P, Das S, et al. Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells. Sci Rep, 2016, 6: 20263.
31. Nunes A C. Viral pathogenesis: HCV RNA acts as a miR-122 sponge. Nature Reviews Microbiology, 2015, 13(5): 250.
32. Zhu Mu, Liu Jiafan, Xiao Jia, et al. Lnc-mg is a long non-coding RNA that promotes myogenesis. Nat Commun, 2017, 8: 14718.
33. Pratt T, Price D J. Junk DNA used in cerebral cortical evolution. Neuron, 2016, 90(6): 1141-1143.
34. Su Zhaoran, Zhi Xiaofei, Zhang Qun, et al. LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier. FEBS Lett, 2016, 590(9): 1354-1364.
35. Liu Qiang, Zhang Xin, Hu Xiaoqing, et al. Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 ‘sponge’ in human cartilage degradation. Sci Rep, 2016, 6: 22572.
36. Shen S, Jiang H, Bei Y, et al. Long non-coding RNAs in cardiac remodeling, Cell Physiol Biochem, 2017, 41(5): 1830-1837.
37. Wang Kun, Long Bo, Zhou Luyu, et al. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun, 2014, 5: 3596.
38. Wang Kun, Long Bo, Liu Fang, et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J, 2016, 37(33): 2602-2611.
39. Liu X H, Sun M, Nie F Q, et al. Lnc RNA HOTAIR funclions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer, 2014, 13: 92.
40. Tang J, Zhuo H, Zhang X, et al. A novel biomarker Linc00974 interacting with KRTl9 promotes proliferation and metastasis in hepatocellular carcinoma. Cell Death & Disease, 2014, 5: e1549.
41. Conte F, Fiscon G, Chiara M, et al. Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer. PLoS One, 2017, 12(2): e0171661.
42. Zhang Shilong, Dong Xinxin, Ji Tongyu, et al. Long non-coding RNA UCA1 promotes cell progression by acting as a competing endogenous RNA of ATF2 in prostate cancer. Am J Transl Res, 2017, 9(2): 366-375.
43. Chiu Y C, Wang Liju, Lu T P, et al. Differential correlation analysis of glioblastoma reveals immune ceRNA interactions predictive of patient survival. BMC Bioinformatics, 2017, 18(1): 132.

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