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Published on: December 21, 2019
RBM47 inhibits hepatocellular carcinoma progression by targeting UPF1 as a DNA/RNA regulator
1Department of Pathophysiology, School of Basic Medical Sciences, Weifang Medical University, Weifang, 261053, China.
Abstract:
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.
Insights
RNA-binding motif protein 47 (RBM47) suppresses hepatocellular carcinoma (HCC) growth and metastasis. RBM47 upregulates the tumor suppressor UPF1 at both transcriptional and posttranscriptional levels, highlighting its role in HCC progression.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Hepatocellular carcinoma (HCC) progression mechanisms, including growth and metastasis, are poorly understood.
- Molecular dysregulation significantly impacts cellular signaling pathways in HCC.
- The role of RNA-binding motif protein 47 (RBM47) as a tumor regulator in HCC is currently ambiguous.
Purpose of the Study:
- To investigate the function of RBM47 in hepatocellular carcinoma (HCC).
- To elucidate the molecular mechanisms by which RBM47 influences HCC tumor behaviors.
- To determine if RBM47 acts as a tumor suppressor or promoter in HCC.
Main Methods:
- In vitro assays to assess RBM47's influence on tumor behaviors.
- In vivo xenograft models to evaluate RBM47's effect on tumor growth and metastasis.
- Analysis of RBM47's interaction with UPF1 mRNA and its transcriptional regulation.
Main Results:
- RBM47 demonstrated an inhibitory effect on HCC tumor behaviors in vitro.
- RBM47 suppressed xenograft tumor growth and metastasis in vivo.
- RBM47 was found to positively regulate Upframeshift 1 (UPF1) expression.
- RBM47 enhances UPF1 mRNA stability by binding to its 3'UTR and promotes UPF1 transcription.
Conclusions:
- RBM47 functions as a tumor suppressor in hepatocellular carcinoma (HCC).
- RBM47 exerts its tumor-suppressive role by upregulating UPF1.
- RBM47 acts as a DNA/RNA binding protein, regulating UPF1 at both transcriptional and posttranscriptional levels.
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