MicroRNA-223 Decreases Cell Proliferation, Migration, Invasion, and Enhances Cell Apoptosis in Childhood Acute Lymphoblastic Leukemia Via Targeting Forkhead Box O 1

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2020 Sep 23

PMID 32964916

Citations 5

Authors

Chunyu Li

Tana Zhao

Lei Nie

Yanhong Zou

Quan Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: Acute lymphoblastic leukemia (ALL) is a frequent malignancy in childhood. The present study was aimed to investigate the effect of miR-223 in ALL and its underlying molecular mechanisms.

Methods: The mRNA expression of miR-223 and FOXO1 was detected by qRT-RCR in ALL children. The correlation between miR-223 and clinical indexes of ALL was determined. CCRF-CEM and NALM-6 cells were transfected with miR-223 mimic and miR-223 inhibitor, respectively. The proliferation, apoptosis, invasion and migration of CCRF-CEM and NALM-6 cells were measured by MTT, flow cytometry and transwell assay. The protein expression of FOXO1 was detected by Western blot. Additionally, dual-luciferase reporter and RNA pull-down assay were performed to investigate the target gene of miR-223 and validate their targeting relationship.

Results: The mRNA expression of miR-223 was markedly down-regulated in ALL, but FOXO1 was up-regulated. The protein expression of FOXO1 was highly expressed in CCRF-CEM and NALM-6 cells. The expression of miR-223 was related to WBC, PLT, RBC and risk stratification. Overexpression of miR-223 not only inhibited cell proliferation, migration and invasion, but also induced cell apoptosis. Importantly, FOXO1 was a target gene of miR-223 in ALL cells. Silencing of FOXO1 reversed the effects of miR-223 inhibitor on cell proliferation, migration, invasion and apoptosis in ALL.

Conclusions: miR-223 could inhibit cell proliferation, migration and invasion, and promote apoptosis by targeting FOXO1 in ALL.

Citing Articles

Immune checkpoints and ncRNAs: pioneering immunotherapy approaches for hematological malignancies.

Anvari S, Nikbakht M, Vaezi M, Amini-Kafiabad S, Ahmadvand M Cancer Cell Int. 2024; 24(1):410.

PMID: 39702293 PMC: 11660508. DOI: 10.1186/s12935-024-03596-8.

The Promising Role of Non-Coding RNAs as Biomarkers and Therapeutic Targets for Leukemia.

Ghazimoradi M, Karimpour-Fard N, Babashah S Genes (Basel). 2023; 14(1).

PMID: 36672872 PMC: 9859176. DOI: 10.3390/genes14010131.

A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia.

Drozak P, Brylinski L, Zawitkowska J Cancers (Basel). 2022; 14(21).

PMID: 36358802 PMC: 9659124. DOI: 10.3390/cancers14215384.

MicroRNAs and the Diagnosis of Childhood Acute Lymphoblastic Leukemia: Systematic Review, Meta-Analysis and Re-Analysis with Novel Small RNA-Seq Tools.

Kyriakidis I, Kyriakidis K, Tsezou A Cancers (Basel). 2022; 14(16).

PMID: 36010971 PMC: 9406077. DOI: 10.3390/cancers14163976.

MAGI2-AS3 restrains proliferation, glycolysis, and triggers apoptosis in acute lymphoblastic leukemia via regulating miR-452-5p/FOXN3 pathway.

Chen X, Dou B, An J, Feng S, Liu N, Sheng G Iran J Basic Med Sci. 2022; 25(1):46-52.

PMID: 35656441 PMC: 9118285. DOI: 10.22038/IJBMS.2021.58963.13095.

References

Xiao Y, Su C, Deng T . miR-223 decreases cell proliferation and enhances cell apoptosis in acute myeloid leukemia via targeting FBXW7. Oncol Lett. 2016; 12(5):3531-3536. PMC: 5103979. DOI: 10.3892/ol.2016.5115. View

Qi W, Yan Y, Pfeifer D, Donner V Gromoff E, Wang Y, Maier W . C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation. PLoS Genet. 2017; 13(5):e1006801. PMC: 5467913. DOI: 10.1371/journal.pgen.1006801. View

Oliveira L, Schiavinato J, Fraguas M, Lucena-Araujo A, Haddad R, Araujo A . Potential roles of microRNA-29a in the molecular pathophysiology of T-cell acute lymphoblastic leukemia. Cancer Sci. 2015; 106(10):1264-77. PMC: 4637998. DOI: 10.1111/cas.12766. View

Vogt P, Jiang H, Aoki M . Triple layer control: phosphorylation, acetylation and ubiquitination of FOXO proteins. Cell Cycle. 2005; 4(7):908-13. DOI: 10.4161/cc.4.7.1796. View

Kohrer S, Havranek O, Seyfried F, Hurtz C, Coffey G, Kim E . Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition. Leukemia. 2016; 30(6):1246-54. PMC: 5459356. DOI: 10.1038/leu.2016.9. View

Jia C, Li H, Zhu X, Dong Y, Fu D, Zhao Q . MiR-223 suppresses cell proliferation by targeting IGF-1R. PLoS One. 2011; 6(11):e27008. PMC: 3206888. DOI: 10.1371/journal.pone.0027008. View

Pui C, Robison L, Look A . Acute lymphoblastic leukaemia. Lancet. 2008; 371(9617):1030-43. DOI: 10.1016/S0140-6736(08)60457-2. View

Lu X, Jiang Q, Huang P, Li G, Zhang W, Zhao X . [Preliminary analysis of aberrant expression of plasma miR-223 in pediatric acute lymphoblastic leukemia with a direct RT-PCR assay]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013; 21(1):68-72. DOI: 10.7534/j.issn.1009-2137.2013.01.015. View

Bhatia S, Kaul D, Varma N . Potential tumor suppressive function of miR-196b in B-cell lineage acute lymphoblastic leukemia. Mol Cell Biochem. 2010; 340(1-2):97-106. DOI: 10.1007/s11010-010-0406-9. View

10.

Mosakhani N, Missiry M, Vakkila E, Knuutila S, Vakkila J . Low Expression of miR-18a as a Characteristic of Pediatric Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol. 2017; 39(8):585-588. DOI: 10.1097/MPH.0000000000000921. View

11.

de Oliveira J, Scrideli C, Brassesco M, Yunes J, Brandalise S, Tone L . MiR-708-5p is differentially expressed in childhood acute lymphoblastic leukemia but not strongly associated to clinical features. Pediatr Blood Cancer. 2014; 62(1):177-8. DOI: 10.1002/pbc.25222. View

12.

Lin S, Ptasinska A, Chen X, Shrestha M, Assi S, Chin P . A FOXO1-induced oncogenic network defines the AML1-ETO preleukemic program. Blood. 2017; 130(10):1213-1222. PMC: 5606002. DOI: 10.1182/blood-2016-11-750976. View

13.

Wu S, Hao Y, Qiu J, Zhang D, Yu C, Li W . High expression of long non-coding RNA CCAT2 indicates poor prognosis of gastric cancer and promotes cell proliferation and invasion. Minerva Med. 2017; 108(4):317-323. DOI: 10.23736/S0026-4806.17.04703-6. View

14.

Piatopoulou D, Avgeris M, Marmarinos A, Xagorari M, Baka M, Doganis D . miR-125b predicts childhood acute lymphoblastic leukaemia poor response to BFM chemotherapy treatment. Br J Cancer. 2017; 117(6):801-812. PMC: 5589998. DOI: 10.1038/bjc.2017.256. View

15.

Capparelli C, Whitaker-Menezes D, Guido C, Balliet R, Pestell T, Howell A . CTGF drives autophagy, glycolysis and senescence in cancer-associated fibroblasts via HIF1 activation, metabolically promoting tumor growth. Cell Cycle. 2012; 11(12):2272-84. PMC: 3383589. DOI: 10.4161/cc.20717. View

16.

Zhu H . Targeting forkhead box transcription factors FOXM1 and FOXO in leukemia (Review). Oncol Rep. 2014; 32(4):1327-34. DOI: 10.3892/or.2014.3357. View

17.

Guttilla I, White B . Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem. 2009; 284(35):23204-16. PMC: 2749094. DOI: 10.1074/jbc.M109.031427. View

18.

Ultimo S, Martelli A, Zauli G, Vitale M, Calin G, Neri L . Roles and clinical implications of microRNAs in acute lymphoblastic leukemia. J Cell Physiol. 2017; 233(8):5642-5654. DOI: 10.1002/jcp.26290. View

19.

Wu L, Li H, Jia C, Cheng W, Yu M, Peng M . MicroRNA-223 regulates FOXO1 expression and cell proliferation. FEBS Lett. 2012; 586(7):1038-43. DOI: 10.1016/j.febslet.2012.02.050. View

20.

Brix N, Rosthoj S . Bone marrow involvement is not manifest in the early stages of childhood acute lymphoblastic leukaemia. Dan Med J. 2014; 61(8):A4883. View