Aberrant expression of long noncoding RNAs (lncRNAs) is associated with various human cancers. However, the role of lncRNAs in Bcr-Abl-mediated chronic myeloid leukemia (CML) is unknown. In this study, we performed a comprehensive analysis of lncRNAs in human CML cells using an lncRNA cDNA microarray and identified an lncRNA termed lncRNA-BGL3 that acted as a key regulator of Bcr-Abl-mediated cellular transformation. Notably, we observed that lncRNA-BGL3 was highly induced in response to disruption of Bcr-Abl expression or by inhibiting Bcr-Abl kinase activity in K562 cells and leukemic cells derived from CML patients. Ectopic expression of lncRNA-BGL3 sensitized leukemic cells to undergo apoptosis and inhibited Bcr-Abl-induced tumorigenesis. Furthermore, transgenic (TG) mice expressing lncRNA-BGL3 were generated. We found that TG expression of lncRNA-BGL3 alone in mice was sufficient to impair primary bone marrow transformation by Bcr-Abl. Interestingly, we identified that lncRNA-BGL3 was a target of miR-17, miR-93, miR-20a, miR-20b, miR-106a and miR-106b, microRNAs that repress mRNA of phosphatase and tensin homolog (PTEN). Further experiments demonstrated that lncRNA-BGL3 functioned as a competitive endogenous RNA for binding these microRNAs to cross-regulate PTEN expression. Additionally, our experiments have begun to address the mechanism of how lncRNA-BGL3 is regulated in the leukemic cells and showed that Bcr-Abl repressed lncRNA-BGL3 expression through c-Myc-dependent DNA methylation. Taken together, these results reveal that Bcr-Abl-mediated cellular transformation critically requires silence of tumor-suppressor lncRNA-BGL3 and suggest a potential strategy for the treatment of Bcr-Abl-positive leukemia.
High-pressure granulites are generally characterized by the absence of orthopyroxene. However, orthopyroxene is reported in a few high-pressure, felsic-metapelitic granulites, such as the Huangtuling felsic high-pressure granulite in the North Dabie metamorphic core complex in east-central China, which rarely preserves the high-pressure granulite facies assemblage of garnet + orthopyroxene + biotite + plagioclase + K-feldspar + quartz. To investigate the effects of bulk-rock composition on the stability of orthopyroxene-bearing, high-pressure granulite facies assemblages in the NCKFMASHTO (Na 2 O-CaO-K 2 O-FeO-MgO-Al 2 O 3 -SiO 2 -H 2 O-TiO 2 -Fe 2 O 3 ) system, a series of P-T-X pseudosections based on the melt-reintegrated composition of the Huangtuling felsic high-pressure granulite were constructed. Calculations demonstrate that the orthopyroxene-bearing, high-pressure granulite facies assemblages are restricted to low X ) < 0.35, mole proportion] or high X Mg [MgO/(MgO + FeO) > 0.85] felsic-metapelitic rock types. This study also reveals that the X Al values in the residual felsic-metapelitic, high-pressure granulites could be significantly reduced by a high proportion of melt loss. We suggest that orthopyroxene-bearing, high-pressure granulites occur in residual overthickened crustal basement under continental subduction-collision zones and arc-continent collision belts.
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