title: An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-α and cAMP/PKA pathways.
abstract: MicroRNAs (miRNAs) are a family of 19-24 nucleotide non-coding RNAs with posttranscriptional regulatory functions. The involvement of miRNAs in normal hematopoiesis implies that deregulated miRNAs might contribute to leukemogenesis. To date, although certain miRNAs have been established a clear oncogenic role in hematological malignancies, other individual miRNAs potentially involved in human leukemogenesis still remain elusive. In this report, we showed that miR-142-3p was upregulated in human T-leukemic cell lines and primary T-leukemic cells isolated from T-cell acute lymphoblastic leukemia (T-ALL) patients and its expressive levels were correlated with patients' prognosis. Such an oncogenic role of miR-142-3p could be explained by its targeting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and glucocorticoid receptor alpha (GRα). High levels of miR-142-3p resulted in low levels of cAMP and weak activity of PKA, thus relieving the inhibitory effect of PKA on T-leukemic cell proliferation. Meanwhile, miR-142-3p decreased GRα protein expression by directly targeting the 3'-untranslational region of GRα mRNA, leading to glucocorticoid resistance. Transfection of the miR-142-3p inhibitor effectively converted glucocorticoid resistance, because of the resultant increase of GRα expression and PKA activity. These findings suggest that miR-142-3p is critical in T-cell leukemogenesis and may serve as a potential therapeutic target in T-ALL patients.
authors: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China.
authors: M
authors: M
authors: Lv
authors: X
authors: X
authors: Zhang
authors: H
authors: H
authors: Jia
authors: D
authors: D
authors: Li
authors: B
authors: B
authors: Zhang
authors: H
authors: H
authors: Zhang
authors: M
authors: M
authors: Hong
authors: T
authors: T
authors: Jiang
authors: Q
authors: Q
authors: Jiang
authors: J
authors: J
authors: Lu
authors: X
authors: X
authors: Huang
authors: B
authors: B
authors: Huang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases