MicroRNA-211 attenuates cell proliferation in T-cell lymphoblastic lymphoma through targeting TCF12
| Autor: | Licai An, Xijing Li, Jing Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cancer Research Methyltransferase DGCR8 T cell Apoptosis Precursor T-Cell Lymphoblastic Leukemia-Lymphoma chemistry.chemical_compound Mice microRNA medicine Basic Helix-Loop-Helix Transcription Factors Biomarkers Tumor Tumor Cells Cultured Gene silencing Animals Humans Cell Proliferation biology Cell growth Lymphoblastic lymphoma Hematology medicine.disease Prognosis Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Survival Rate MicroRNAs medicine.anatomical_structure Oncology chemistry biology.protein Cancer research Female N6-Methyladenosine |
| Zdroj: | Leukemia research. 110 |
| ISSN: | 1873-5835 |
| Popis: | T-cell lymphoblastic lymphoma (T-LBL) is a class of highly aggressive hematologic neoplasms originating from progenitor T-lymphocytes. MicroRNA (miRNA) is an endogenous RNA molecule with 22 nucleotides in length. Accumulated evidence suggests that miRNA functions as a key regulator in human cancer. Herein, by in silico analysis, we found that miR-211 was a decreased miRNA in T-LBL in high-throughput sequencing data, which was subsequently verified in our cohort. Low miR-211 was closely correlated with bulky disease, high ann arbor stage, relapse and poor prognosis. miR-211 was regulated by N6-methyladenosine (m6A) modification, specifically, m6A methyltransferase METTL14 methylated primary miR-211 (pri-miR-211), expediting pri-miR-211 processing via recruiting DGCR8. Functionally, miR-211 overexpression significantly reduced T-LBL cell viability, DNA synthesis rate and spheroid formation ability, whereas silencing of miR-211 had the opposite effects. In addition, we established the xenograft tumor model and found that miR-211 remarkably inhibited tumor growth in vivo. Further, TCF12 was the direct target of miR-211, miR-211 bound to TCF12 mRNA 3`-untranslated region (UTR) and increased its decay, overexpression of TCF12 could effectively rescue the weakened malignant behavior of T-LBL cells caused by miR-211 overexpression. Collectively, our data clearly demonstrate that miR-211 is a novel tumor suppressor in T-LBL, targeting of miR-211/TCF12 axis may be a potential treatment for T-LBL patients. |
| Databáze: | OpenAIRE |
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