MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p> T-cell acute lymphoblastic leukemia is a hematologic malignancy characterized by T-cell proliferation, and in many cases, the ectopic expression of the oncogenic transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1). MicroRNA-7 has been shown to play a critical role in proliferation, migration, and treatment sensitivity in a diverse array of cancers. In this study, we sought to establish a novel link between microRNA-7 and T-cell acute lymphoblastic leukemia oncogenesis. </jats:p></jats:sec><jats:sec><jats:title>Material and Method:</jats:title><jats:p> To do so, we characterized gene expression of microRNA-7 as well as TAL1 in both T-cell acute lymphoblastic leukemia patient-derived tissue and cell lines, as well as performing functional luciferase assays to assess microRNA-7 binding to the TAL1 3′-untranslated region. We also performed growth, apoptosis, and migration experiments using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide, Annexin V, and transwell assays in the context of microRNA-7 overexpression. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We found that microRNA-7 expression is attenuated and inversely correlated with TAL1 expression in TAL1 + T-cell acute lymphoblastic leukemia cells. Additionally, microRNA-7 directly targets and suppresses TAL1 levels. Finally, microRNA-7 overexpression reduces growth, motility, and migration while inducing apoptosis in T-cell acute lymphoblastic leukemia cells, phenotypes that can be rescued by concomitant overexpression of TAL1. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> These results indicate that microRNA-7 functions as a potent tumor suppressor by inhibiting the oncogene TAL1 and suggest microRNA-7 could function as a prognostic biomarker and possible therapeutic in the clinical management of T-cell acute lymphoblastic leukemia. </jats:p></jats:sec>

Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11

“…In addition, miR-7-5p can increase the sensitivity of breast carcinoma cells to adriamycin after inhibiting the epidermal growth factor (EGF) receptor/PI3K signaling pathway [ 43 ], and can inhibit the proliferation and metastasis of osteosarcoma cells by targeting insulin-like growth factor 1 receptor [ 44 ]. Another study revealed that miR-7-5p inhibits the proliferation of T-cell acute lymphoblastic leukemia by targeting the oncogene T-cell acute leukemia protein 1 [ 45 ]. More essentially, the anticancer effects of miR-7-5p have been reported in other carcinomas.…”

Role of MicroRNA-7 (MiR-7) in Cancer Physiopathology

“…It was shown that there are several p53-dependent miRNAs induced in response to DNA damage in CLL, proposing that the miRNoma for the identification of the dependent DNA damage response machinery stems from p53 [ 118 ]. In ALL (acute lymphoblastic leukemia) of T lymphocytes, it was reported that the overexpression of miR-7 is capable of suppressing TAL1 levels and reducing growth, mobility, and migration, as well as promoting the induction of apoptosis, allowing it to play a potential role as tumor suppressor [ 119 ]…”

MiR-7 in Cancer Development

“…In T-ALL, miR-7 was found to bind to TAL1 , coding for T-cell acute lymphocytic leukaemia protein. In T-ALL, expression of miR-7 is often attenuated, while TAL1 expression is increased and solicitates cell proliferation [ 80 ]. In Non-Hodgkin lymphoma cells, miR-7 regulates migration and chemoresistance through KLF4 and YY1 [ 108 ] and miR-7 downregulation can increase the aggressiveness of follicular lymphoma by FasL upregulation in macrophages which modulate immunosuppressive stroma [ 174 ].…”