Project description:By RIP sequencing, we determined that RBM47 modulated UPF1 by stabilizing its mRNA and addressed the novel motif in the UPF1 3’UTR with direct binding.
Project description:Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits. Cancer cells transduced with doxycycline-inducible wildtype RBM47 or the RBM47-I281fs mutant, treated with increasing concentrations of doxycycline.
Project description:Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits.
Project description:The mechanisms by which the tumor behaviors of hepatocellular carcinoma (HCC) support growth and metastasis remain largely unknown, and it has become increasingly apparent that molecular dysregulation is of considerable importance for cellular signaling pathways. Recently, RNA-binding motif protein 47 (RBM47) has been suggested to function as a tumor regulator by acting as an RNA binding protein (RBP), but its role in HCC remains ambiguous. Here, in HCC, we identified that RBM47 had an inhibitory influence on tumor behaviors in vitro and accordingly suppressed the growth and metastasis of xenograft tumors in vivo. Additionally, RBM47 was verified to positively regulate Upframeshift 1 (UPF1), which is a crucial protein involved in the nonsense-mediated RNA decay (NMD) process and was previously determined to be an HCC suppressor. Mechanistically, the stability of UPF1 mRNA was demonstrated to be enhanced with its 3'UTR bound by RBM47, which acted as an RNA binding protein. Meanwhile, RBM47 was also proven to promote the transcription of UPF1 as a transcription factor. Taken together, we concluded that RBM47 functioned as a tumor suppressor by upregulating UPF1, acting as a DNA/RNA binding protein at the transcriptional and posttranscriptional levels.
| S-EPMC9279423 | biostudies-literature
Project description:RBM47 Inhibits Hepatocellular Carcinoma Progression as a DNA/RNA Regulator
| PRJNA833052 | ENA
Project description:RBM47 Inhibits Hepatocellular Carcinoma Progression as a DNA/RNA Regulator
Project description:ABSTRACT RNA binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers, but scarcely studied in nasopharyngeal carcinoma (NPC). Here, we compare the mRNA levels of 29 RBMs between 87 NPC and 10 control samples. We find that RBM47 is frequently upregulated in NPC specimens and its high expression is associated with poor prognosis of patients with NPC. Biological experiments show that RBM47 plays an oncogenic role in NPC cells. Mechanically, RBM47 binds to the promoter and regulates the transcription of BCAT1 and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells. Moreover, transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-mRNA, including those cancer-related, to a large extent in NPC cells. Furthermore, RBM47 binds to hnRNPM and cooperativelyjointly regulates multiple splicing events in NPC cells. In addition, we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells. Taken together, our study shows that RBM47 promotes the progression of NPC through multiple pathways, acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM. Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC. Keywords RBM47, BCAT1, Alternative splicing, hnRNPM, Nasopharyngeal Carcinoma (NPC)