open access

Vol 58, No 3 (2020)
Original paper
Submitted: 2020-05-13
Accepted: 2020-08-19
Published online: 2020-09-07
Get Citation

Upregulated miR-96-5p inhibits cell proliferation by targeting HBEGF in T-cell acute lymphoblastic leukemia cell line

Kaihong Xu1, Xiao Yan1, Guifang Ouyang1, Jinyi Feng2, Lilin Ye2, Xuezhen Hu3, Dingsheng Liu2
·
Pubmed: 32893872
·
Folia Histochem Cytobiol 2020;58(3):219-226.
Affiliations
  1. Department of Hematology, Ningbo First Hospital, Ningbo City, Zhejiang Province, 315000, China
  2. Department of Oncology and Hematology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai City, 201318, China
  3. Department of Emergency Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China

open access

Vol 58, No 3 (2020)
ORIGINAL PAPERS
Submitted: 2020-05-13
Accepted: 2020-08-19
Published online: 2020-09-07

Abstract

Introduction. microRNAs (miRNAs) are critical for tumorigenesis and progression of T-cell acute lymphoblastic leukemia (T-ALL). MiR-96-5p has been shown to play important roles in the development of many cancers, but its roles in T-ALL have yet not been studied.

Materials and methods. miR-96-5p expression was detected in T-leukemic cells from peripheral blood of 30 patients with T-ALL using real-time quantitative PCR (RT-qPCR). TargetScan database was utilized to identify the target genes for miR-96-5p, and their target relationship was verified by western blot, dual luciferase reporter assay and RT-qPCR. The effects of miR-96-5p on the viability and proliferation of T-leukemic cells (Jurkat cells) were respectively determined using MTT and BrdU incorporation assays. Results. miR-96-5p presented low expression levels by qPCR in peripheral blood of T-ALL patients compared to healthy volunteers. Upregulated miR-96-5p by miR-96-5p mimic transfection markedly inhibited the viability and proliferation of Jurkat cells. Furthermore, miR-96-5p negatively regulated the expression of its target gene, HBEGF. The decreased viability and proliferation of Jurkat cells caused by miR-96-5p over-expression was suppressed after the introduction of HBEGF plasmid. Conclusions. The presented study showed that upregulation of miR-96-5p inhibited the viability and proliferation of Jurkat T-leukemic cells through suppressing HBEGF expression. Our study provides a novel sight for understanding the pathological mechanism of T-ALL and suggests that miR-96-5p may be a potential biomarker for the therapy and diagnosis of T-ALL.

Abstract

Introduction. microRNAs (miRNAs) are critical for tumorigenesis and progression of T-cell acute lymphoblastic leukemia (T-ALL). MiR-96-5p has been shown to play important roles in the development of many cancers, but its roles in T-ALL have yet not been studied.

Materials and methods. miR-96-5p expression was detected in T-leukemic cells from peripheral blood of 30 patients with T-ALL using real-time quantitative PCR (RT-qPCR). TargetScan database was utilized to identify the target genes for miR-96-5p, and their target relationship was verified by western blot, dual luciferase reporter assay and RT-qPCR. The effects of miR-96-5p on the viability and proliferation of T-leukemic cells (Jurkat cells) were respectively determined using MTT and BrdU incorporation assays. Results. miR-96-5p presented low expression levels by qPCR in peripheral blood of T-ALL patients compared to healthy volunteers. Upregulated miR-96-5p by miR-96-5p mimic transfection markedly inhibited the viability and proliferation of Jurkat cells. Furthermore, miR-96-5p negatively regulated the expression of its target gene, HBEGF. The decreased viability and proliferation of Jurkat cells caused by miR-96-5p over-expression was suppressed after the introduction of HBEGF plasmid. Conclusions. The presented study showed that upregulation of miR-96-5p inhibited the viability and proliferation of Jurkat T-leukemic cells through suppressing HBEGF expression. Our study provides a novel sight for understanding the pathological mechanism of T-ALL and suggests that miR-96-5p may be a potential biomarker for the therapy and diagnosis of T-ALL.

Get Citation

Keywords

miR-96-5p; T-cell acute lymphoblastic leukemia; Jurkat T cells; HBEGF

About this article
Title

Upregulated miR-96-5p inhibits cell proliferation by targeting HBEGF in T-cell acute lymphoblastic leukemia cell line

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 58, No 3 (2020)

Article type

Original paper

Pages

219-226

Published online

2020-09-07

Page views

1444

Article views/downloads

931

DOI

10.5603/FHC.a2020.0018

Pubmed

32893872

Bibliographic record

Folia Histochem Cytobiol 2020;58(3):219-226.

Keywords

miR-96-5p
T-cell acute lymphoblastic leukemia
Jurkat T cells
HBEGF

Authors

Kaihong Xu
Xiao Yan
Guifang Ouyang
Jinyi Feng
Lilin Ye
Xuezhen Hu
Dingsheng Liu

References (30)
  1. Malard F, Mohty M. Acute lymphoblastic leukaemia. The Lancet. 2020; 395(10230): 1146–1162.
  2. Jacobson S, Tedder M, Eggert J. Adult Acute Lymphoblastic Leukemia: A Genetic Overview and Application to Clinical Practice. Clin J Oncol Nurs. 2016; 20(6): E147–E154.
  3. Follini E, Marchesini M, Roti G. Strategies to Overcome Resistance Mechanisms in T-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2019; 20(12).
  4. Bongiovanni D, Saccomani V, Piovan E. Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2017; 18(9).
  5. Drobna M, Szarzyńska-Zawadzka B, Dawidowska M. T-cell acute lymphoblastic leukemia from miRNA perspective: Basic concepts, experimental approaches, and potential biomarkers. Blood Rev. 2018; 32(6): 457–472.
  6. Evangelisti C, Chiarini F, McCubrey JA, et al. Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update. Int J Mol Sci. 2018; 19(7).
  7. Maude SL, Teachey DT, Porter DL, et al. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015; 125(26): 4017–4023.
  8. Zhang L, Tang Y, Zhu X, et al. Overexpression of MiR-335-5p Promotes Bone Formation and Regeneration in Mice. J Bone Miner Res. 2017; 32(12): 2466–2475.
  9. Ji Y, Wang D, Zhang B, et al. MiR-361-3p inhibits β-amyloid accumulation and attenuates cognitive deficits through targeting BACE1 in Alzheimer's disease. J Integr Neurosci. 2019; 18(3): 285–291.
  10. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281–297.
  11. Sandoval-Bórquez A, Polakovicova I, Carrasco-Véliz N, et al. MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer. Clin Epigenetics. 2017; 9: 114.
  12. Tutar Y. miRNA and cancer; computational and experimental approaches. Curr Pharm Biotechnol. 2014; 15(5): 429.
  13. Nucera S, Giustacchini A, Boccalatte F, et al. miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia. Cancer Cell. 2016; 29(6): 905–921.
  14. Yang XY, Sheng Ye. miR-101 Represses T-Cell Acute Lymphoblastic Leukemia by Targeting CXCR7/STAT3 Axis. Oncol Res. 2019; 27(9): 997–1006.
  15. Huang W, Wang WT, Fang Ke, et al. MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47. Mol Cancer. 2018; 17(1): 12.
  16. Iwai N, Yasui K, Tomie A, et al. Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma. Int J Oncol. 2018; 53(1): 237–245.
  17. Hao H, Liu Q, Wu D, et al. Tetrahydropalmatine reduces cell death and improves functional recovery after traumatic spinal cord injury in rats. Trop J Pharm Res. 2019; 18(5): 703–711.
  18. Gao XH, Zhang YL, Zhang ZY, et al. MicroRNA-96-5p represses breast cancer proliferation and invasion through Wnt/β-catenin signaling via targeting CTNND1. Sci Rep. 2020; 10(1): 44.
  19. Yang CC, Chang KW. Eicosanoids and HB-EGF/EGFR in cancer. Cancer Metastasis Rev. 2018; 37(2-3): 385–395.
  20. Kunami N, Yotsumoto F, Ishitsuka K, et al. Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute lymphoblastic leukemia. Anticancer Res. 2011; 31(7): 2483–2488.
  21. Bond J, Marchand T, Touzart A, et al. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. Haematologica. 2016; 101(6): 732–740.
  22. Rashed WM, Hamza MM, Matboli M, et al. MicroRNA as a prognostic biomarker for survival in childhood acute lymphoblastic leukemia: a systematic review. Cancer Metastasis Rev. 2019; 38(4): 771–782.
  23. Zhang H, Chen R, Shao J. MicroRNA-96-5p Facilitates the Viability, Migration, and Invasion and Suppresses the Apoptosis of Cervical Cancer Cells byNegatively Modulating SFRP4. Technol Cancer Res Treat. 2020; 19: 1533033820934132.
  24. Alinari L, Mahasenan KV, Yan F, et al. Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation. Blood. 2015; 125(16): 2530–2543.
  25. Mensah AA, Cascione L, Gaudio E, et al. Bromodomain and extra-terminal domain inhibition modulates the expression of pathologically relevant microRNAs in diffuse large B-cell lymphoma. Haematologica. 2018; 103(12): 2049–2058.
  26. Wei LQ, Liang HT, Qin DC, et al. MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF. Tumour Biol. 2014; 35(12): 12427–12434.
  27. Rao L, Giannico D, Leone P, et al. HB-EGF-EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma. Cancers (Basel). 2020; 12(1).
  28. Shimura T, Yoshida M, Fukuda S, et al. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion. BMC Cancer. 2012; 12: 205.
  29. Tian XP, Huang WJ, Huang HQ, et al. Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma. Leukemia. 2019; 33(10): 2454–2465.
  30. Yu S, Geng Q, Ma J, et al. Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on Runx2-induced osteogenic differentiation. Cell Death Dis. 2013; 4: e868.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl