6 research outputs found
MicroRNA-144 acts as a tumor suppressor by targeting Rho-associated coiled-coil containing protein kinase 1 in osteosarcoma cells
Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer
Abstract Resistance to tamoxifen is a clinically major challenge in breast cancer treatment. Although downregulation of estrogen receptorâalpha (ERα) is the dominant mechanism of tamoxifen resistance, the reason for ERα decrease during tamoxifen therapy remains elusive. Herein, we reported that Spaltâlike transcription factor 2 (SALL2) expression was significantly reduced during tamoxifen therapy through transcription profiling analysis of 9 paired primary preâtamoxifenâtreated and relapsed tamoxifenâresistant breast cancer tissues. SALL2 transcriptionally upregulated ESR1 and PTEN through directly binding to the DNA promoters. By contrast, silencing SALL2 induced downregulation of ERα and PTEN and activated the Akt/mTOR signaling, resulting in estrogenâindependent growth and tamoxifen resistance in ERαâpositive breast cancer. Furthermore, hypermethylation of SALL2 promoter was found in tamoxifenâresistant breast cancer. Importantly, in vivo experiments showed that DNA methyltransferase inhibitorâmediated SALL2 restoration resensitized tamoxifenâresistant breast cancer to tamoxifen therapy. These findings shed light on the mechanism of SALL2 in regulation of ER and represent a potential clinical signature that can be used to categorize breast cancer patients who may benefit from coâtherapy with tamoxifen and DNMT inhibitor
Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma
Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs)