Upregulated miR-96-5p inhibits cell proliferation by targeting HBEGF in T-cell acute lymphoblastic leukemia cell line
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.
Keywords: miR-96-5pT-cell acute lymphoblastic leukemiaJurkat T cellsHBEGF
References
- Malard F, Mohty M. Acute lymphoblastic leukaemia. The Lancet. 2020; 395(10230): 1146–1162.
- 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.
- Follini E, Marchesini M, Roti G. Strategies to Overcome Resistance Mechanisms in T-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2019; 20(12).
- Bongiovanni D, Saccomani V, Piovan E. Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2017; 18(9).
- 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.
- 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).
- 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.
- 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.
- 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.
- Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281–297.
- 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.
- Tutar Y. miRNA and cancer; computational and experimental approaches. Curr Pharm Biotechnol. 2014; 15(5): 429.
- 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.
- Yang XY, Sheng Ye. miR-101 Represses T-Cell Acute Lymphoblastic Leukemia by Targeting CXCR7/STAT3 Axis. Oncol Res. 2019; 27(9): 997–1006.
- 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.
- 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.
- 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.
- 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.
- Yang CC, Chang KW. Eicosanoids and HB-EGF/EGFR in cancer. Cancer Metastasis Rev. 2018; 37(2-3): 385–395.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.