MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1

Abstract

The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

<p>Alteration in Expression of miR-32 and FBXW7 Tumor Suppressor in Plasma Samples of Patients with T-cell Acute Lymphoblastic Leukemia</p>

“…22,23 It has been shown the expression levels of miR-181a, miR-128-3P and miR-142-3p were significantly up-regulated in T-ALL patients, 1,4,24 whereas miR-204, miR-101 and miR-193b-3p were down-regulated. 2,24,25 Some studies have indicated that FBXW7 dysregulates important signaling pathways including Notch1 and Notes: a Targeting of FBXW7 is confirmed by the software. b Targeting of FBXW7 is not confirmed by the software.…”

“…Introduction T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy results from leukemic transformation of developing thymocytes, 1,2 representing nearly 25% of adult and 10-15% of childhood ALL cases. 2,3 Several cytogenetic abnormalities and genetic aberrations have been associated with the etiology of T-ALL. 1,4 Some functions including self-renewal, proliferation and survival, and blocked differentiation of precursor T cells are affected by these genetic aberrations.…”

miR‑101 regulates the cell proliferation and apoptosis in diffuse large B‑cell lymphoma by targeting MEK1 via regulation of the ERK/MAPK signaling pathway

“…In addition to lymphoma, the relationship between miR-101 and the incidence of lymphoblastic leukemia has also been reported. Qian et al (32) showed that the expression of miR-101 in the peripheral blood of patients with lymphoblastic leukemia was decreased significantly compared with healthy individuals. In addition, they also found that the expression of miR-101 in the peripheral blood cells of patients with acute T lymphoblastic leukemia was significantly less than miR-101 expression in the healthy thymus and bone marrow cells.…”

“…In addition, the expression of the anti-apoptotic factor, Bcl-2, was significantly reduced, lymphoma cell proliferation was significantly decreased, and apoptosis was significantly increased. Qian et al (32) showed that in the process of the pathogenesis of lymphocytic leukemia, miR-101 acts as a tumor suppressor. Moreover, overexpression of miR-101 was found to decrease the proliferation and invasion of Jurkat lymphocytic leukemia cells, significantly increase apoptosis, and increase the sensitivity of the chemotherapy drug, doxorubicin, by targeting inhibition of the Notch1 gene.…”

Overexpression of miR-101-2 in donor cells improves the early development of Holstein cow somatic cell nuclear transfer embryos

“…The nuclear donor cell is a crucial factor affecting SCNT embryo quality and the efficiency of SCNT, and many efforts have been made to improve them by improving donor-cell status Mizutani et al, 2015). Furthermore, miR-101 can regulate cell proliferation, the cell cycle, and apoptosis in different cell types (Wang et al, 2014b;Zhou et al, 2015;Qian et al, 2016). Therefore, we detected the apoptosis, cell cycle, and proliferation in donor cells after miR-101-2 overexpression.…”