Identification of CircRNA-lncRNA-miRNA-mRNA Competitive Endogenous RNA Network As Novel Prognostic Markers for Acute Myeloid Leukemia

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2020 Aug 6

PMID 32751923

Citations 49

Authors

Yaqi Cheng

Yaru Su

ShouBi Wang

Yurun Liu

Lin Jin

Qi Wan

Ying Liu

Chaoyang Li

Xuan Sang

Liu Yang

Chang Liu

Zhichong Wang

Affiliations

Soon will be listed here.

Abstract

Background: Acute myeloid leukemia (AML) is one of the most common malignant and aggressive hematologic tumors, and its pathogenesis is associated with abnormal post-transcriptional regulation. Unbalanced competitive endogenous RNA (ceRNA) promotes tumorigenesis and progression, and greatly contributes to tumor risk classification and prognosis. However, the comprehensive analysis of the circular RNA (circRNA)-long non-coding RNA (lncRNA)-miRNA-mRNA ceRNA network in the prognosis of AML is still rarely reported.

Method: We obtained transcriptome data of AML and normal samples from The Cancer Genome Atlas (TCGA), Genotype-tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases, and identified differentially expressed (DE) mRNAs, lncRNAs, and circRNAs. Then, the targeting relationships among lncRNA-miRNA, circRNA-miRNA, and miRNA-mRNA were predicted, and the survival related hub mRNAs were further screened by univariate and multivariate Cox proportional hazard regression. Finally, the AML prognostic circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network was established.

Results: We identified prognostic 6 hub mRNAs (TM6SF1, ZMAT1, MANSC1, PYCARD, SLC38A1, and LRRC4) through Cox regression model, and divided the AML samples into high and low risk groups according to the risk score obtained by multivariate Cox regression. Survival analysis verified that the survival rate of the high-risk group was significantly reduced ( < 0.0001). The prognostic ceRNA network of 6 circRNAs, 32 lncRNAs, 8 miRNAs, and 6 mRNAs was established according to the targeting relationship between 6 hub mRNAs and other RNAs.

Conclusion: In this study, ceRNA network jointly participated by circRNAs and lncRNAs was established for the first time. It comprehensively elucidated the post-transcriptional regulatory mechanism of AML, and identified novel AML prognostic biomarkers, which has important guiding significance for the clinical diagnosis, treatment, and further scientific research of AML.

Citing Articles

Identification of the CeRNA axis of circ_0000006/miR-483-5p/KDM2B in the progression of aortic aneurysm to aorta dissection.

Liu Y, Tan X, Wang L, Jin W, He Y, Yan Y BMC Cardiovasc Disord. 2025; 25(1):141.

PMID: 40021969 PMC: 11869725. DOI: 10.1186/s12872-025-04598-8.

AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation.

Bayrak A, Yucel B Medeni Med J. 2024; 39(3):161-168.

PMID: 39350522 PMC: 11572213. DOI: 10.4274/MMJ.galenos.2024.59683.

Abnormal expression of circ_0013958 in patients with acute myocardial infarction (AMI) and its influence on prognosis.

Sun F, Zou S, Li X, Liu X J Cardiothorac Surg. 2024; 19(1):517.

PMID: 39243066 PMC: 11378589. DOI: 10.1186/s13019-024-03036-8.

[Molecular Mechanism of circVRK1 Regulating the Proliferation and Apoptosis of Acute Lymphoblastic Leukemia KOCL44 Cells by Targeting miR-4428].

Zhang H, Wu B, Wang Y Sichuan Da Xue Xue Bao Yi Xue Ban. 2024; 55(4):872-877.

PMID: 39170007 PMC: 11334292. DOI: 10.12182/20240760102.

Identification of Novel DNA Methylation Prognostic Biomarkers for AML With Normal Cytogenetics.

Cardoso C, Pestana D, Gokuladhas S, Marreiros A, OSullivan J, Binnie A JCO Clin Cancer Inform. 2024; 8:e2300265.

PMID: 39052947 PMC: 11371081. DOI: 10.1200/CCI.23.00265.

References

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

Yang Q, Tang Y, Tang C, Cong H, Wang X, Shen X . Diminished LINC00173 expression induced miR-182-5p accumulation promotes cell proliferation, migration and apoptosis inhibition via AGER/NF-κB pathway in non-small-cell lung cancer. Am J Transl Res. 2019; 11(7):4248-4262. PMC: 6684891. View

Mhyre A, Marcondes A, Spaulding E, Deeg H . Stroma-dependent apoptosis in clonal hematopoietic precursors correlates with expression of PYCARD. Blood. 2008; 113(3):649-58. PMC: 2628371. DOI: 10.1182/blood-2008-04-152686. View

Wu D, Wen X, Han X, Wang S, Wang Y, Shen M . Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia. Mol Cell Biol. 2018; 38(20). PMC: 6168983. DOI: 10.1128/MCB.00259-18. View

Huang M, Zhong Z, Lv M, Shu J, Tian Q, Chen J . Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma. Oncotarget. 2016; 7(30):47186-47200. PMC: 5216934. DOI: 10.18632/oncotarget.9706. View

Li W, Zhong C, Jiao J, Li P, Cui B, Ji C . Characterization of hsa_circ_0004277 as a New Biomarker for Acute Myeloid Leukemia via Circular RNA Profile and Bioinformatics Analysis. Int J Mol Sci. 2017; 18(3). PMC: 5372613. DOI: 10.3390/ijms18030597. View

Li X, Yang L, Chen L . The Biogenesis, Functions, and Challenges of Circular RNAs. Mol Cell. 2018; 71(3):428-442. DOI: 10.1016/j.molcel.2018.06.034. View

Cheng D, Xiang Y, Ji L, Lu X . Competing endogenous RNA interplay in cancer: mechanism, methodology, and perspectives. Tumour Biol. 2015; 36(2):479-88. DOI: 10.1007/s13277-015-3093-z. View

de Groot J, Pan X, Meeldijk J, van der Wall E, van Diest P, Moelans C . Validation of DNA promoter hypermethylation biomarkers in breast cancer--a short report. Cell Oncol (Dordr). 2014; 37(4):297-303. DOI: 10.1007/s13402-014-0189-1. View

10.

Han P, Li J, Zhang B, Lv J, Li Y, Gu X . The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling. Mol Cancer. 2017; 16(1):9. PMC: 5237133. DOI: 10.1186/s12943-017-0583-1. View

11.

van der Net J, Janssens A, Eijkemans M, Kastelein J, Sijbrands E, Steyerberg E . Cox proportional hazards models have more statistical power than logistic regression models in cross-sectional genetic association studies. Eur J Hum Genet. 2008; 16(9):1111-6. DOI: 10.1038/ejhg.2008.59. View

12.

Momeni M, Mirzaei M, Zainodini N, Hassanshahi G, Arababadi M . MiR-143 induces expression of AIM2 and ASC in Jurkat cell line. Iran J Immunol. 2013; 10(2):103-9. DOI: IJIv10i2A5. View

13.

Wang C, Tao W, Ni S, Chen Q . Upregulation of lncRNA snoRNA host gene 6 regulates NUAK family SnF1-like kinase-1 expression by competitively binding microRNA-125b and interacting with Snail1/2 in bladder cancer. J Cell Biochem. 2018; 120(1):357-367. DOI: 10.1002/jcb.27387. View

14.

Glazar P, Papavasileiou P, Rajewsky N . circBase: a database for circular RNAs. RNA. 2014; 20(11):1666-70. PMC: 4201819. DOI: 10.1261/rna.043687.113. View

15.

Zhou F, Wang D, Wei W, Chen H, Shi H, Zhou N . Comprehensive profiling of circular RNA expressions reveals potential diagnostic and prognostic biomarkers in multiple myeloma. BMC Cancer. 2020; 20(1):40. PMC: 6966810. DOI: 10.1186/s12885-020-6515-2. View

16.

Chen J, Huang X, Wang W, Xie H, Li J, Hu Z . LncRNA CDKN2BAS predicts poor prognosis in patients with hepatocellular carcinoma and promotes metastasis via the miR-153-5p/ARHGAP18 signaling axis. Aging (Albany NY). 2018; 10(11):3371-3381. PMC: 6286843. DOI: 10.18632/aging.101645. View

17.

Liu Y, Gao X, Tian X . High expression of long intergenic non-coding RNA LINC00662 contributes to malignant growth of acute myeloid leukemia cells by upregulating ROCK1 via sponging microRNA-340-5p. Eur J Pharmacol. 2019; 859:172535. DOI: 10.1016/j.ejphar.2019.172535. View

18.

Wangxia L, Fang Y, Liu Y, Zhao Y, Shi Z, Zhong H . Circular RNA ARHGAP26 is over-expressed and its downregulation inhibits cell proliferation and promotes cell apoptosis in gastric cancer cells. Saudi J Gastroenterol. 2019; 25(2):119-125. PMC: 6457177. DOI: 10.4103/sjg.SJG_283_18. View

19.

Zheng M, Gou R, Zhang W, Nie X, Wang J, Gao L . Screening of prognostic biomarkers for endometrial carcinoma based on a ceRNA network. PeerJ. 2018; 6:e6091. PMC: 6292375. DOI: 10.7717/peerj.6091. View

20.

Li X, Li B, Ran P, Wang L . Identification of ceRNA network based on a RNA-seq shows prognostic lncRNA biomarkers in human lung adenocarcinoma. Oncol Lett. 2018; 16(5):5697-5708. PMC: 6176255. DOI: 10.3892/ol.2018.9336. View