FAMLF is a target of miR-181b in Burkitt lymphoma

Abstract

Burkitt lymphoma (BL) is a highly malignant non-Hodgkin's lymphoma that is closely related to the abnormal expression of genes. Familial acute myelogenous leukemia related factor (FAMLF; GenBank accession No. EF413001.1) is a novel gene that was cloned by our research group, and miR-181b is located in the intron of the FAMLF gene. To verify the role of miR-181b and FAMLF in BL, RNAhybrid software was used to predict target site of miR-181b on FAMLF and real-time quantitative PCR (RQ-PCR) was used to detect expression of miR-181b and FAMLF in BL patients, Raji cells and unaffected individuals. miR-181b was then transfected into Raji and CA46 cell lines and FAMLF expression was examined by RQ-PCR and western blotting. Further, Raji cells viability and proliferation were detected by MTT and clone formation, and Raji cell cycle and apoptosis were detected by flow cytometry. The results showed that miR-181b can bind to bases 21–42 of the FAMLF 5′ untranslated region (UTR), FAMLF was highly expressed and miR-181b was lowly expressed in BL patients compared with unaffected individuals. FAMLF expression was significantly and inversely correlated to miR-181b expression, and miR-181b negatively regulated FAMLF at posttranscriptional and translational levels. A dual-luciferase reporter gene assay identified that the 5′ UTR of FAMLF mRNA contained putative binding sites for miR-181b. Down-regulation of FAMLF by miR-181b arrested cell cycle, inhibited cell viability and proliferation in a BL cell line model. Our findings explain a new mechanism of BL pathogenesis and may also have implications in the therapy of FAMLF-overexpressing BL.

MicroRNAs as Biomarkers of B-cell Lymphoma

“…84 Furthermore, miR-181b was found downregulated in BL cases, and the authors propose that it may function as a tumour suppressor. 85 In an earlier study, significantly lower expression of miR-155, miR-21, and miR-26a was observed between classical BL and cases with intermediate features between BL and DLBCL (DLBCL/BL). 78 Most of the endemic BL cases (>90%) are associated with Epstein-Barr virus (EBV) infection 11,151 that has been shown to regulate several miRNAs, including miR-21, miR-146a, miR-155, miR-10a, and miR-127 in BL cases.…”

“…84 Furthermore, miR-181b was found downregulated in BL cases, and the authors propose that it may function as a tumour suppressor. 85 In an earlier study, significantly lower expression of miR-155, miR-21 , and miR-26a was observed between classical BL and cases with intermediate features between BL and DLBCL (DLBCL/BL). 78…”

LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer

“…MiR-181b can modulate vascular cell adhesion molecule 1 expression and monocyte adhesion in an epidermal growth factor receptor-dependent pathway [ 22 ]. MiR-181b suppressed cell cycle, cell viability and proliferation through down-regulation of FAMLF in burkitt lymphoma cells [ 23 ]. In breast cancer, ectopic expression of miR-181b inhibited the increase of NF-κB level induced by chemokine ligand 18 in cancer cells, thus suppressing cell survival rate and migration [ 24 ].…”

The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer

“…The role of miR-181a and b in Lymphoid cell development has been reviewed by Guarini et al [62], and specific expression profiles linked to the different steps of the maturation/differentiation process largely documented [103,104]. In a recent study, it has been shown that miR-181b directly down-regulates the expression of FAMLF (Familial acute myelogenous leukemia related factor) and inhibits cell viability by binding to the 5 UTR of FAMLF in Burkitt Lymphomas (BL), allowing the authors to suggest a new mechanism of the pathogenesis of BL, and to propose miR-181b as a candidate therapeutic agent in BL forms with FAMLF overexpression [62].…”