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Research Article
Lili Han
Xi'an Jiaotong University Second Affiliated Hospital Department of Oncology
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4964-140X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The post-transcriptional of mRNA expression involved in the hepatocellular carcinoma (HCC) pathogenesis and progression need to be further explored. RBPs, the main undertaker of post-transcriptional regulatory process, has been shown to impact HCC carcinogenesis and progression. However, the role of RBP, RNA-binding motif 45 (RBM45) in hepatocarcinogenesis and its interaction with its potential target mRNA remains entirely unknown. The expression of RBM45 was significantly increased in HCC and was associated with poor clinicopathological features and clinical outcome of HCC patients. RBM45 promoted HCC cells growth, invasion, migration and EMT in vitro and in vivo. Mechanistically, RNA immunoprecipitation sequencing (RIP-seq) approach was utilized to screen the important differentially expressed RBM45 genes in HCC. Furthermore, RIP assay, pull-down assay and mRNA decay assay were carried out to uncover the effect of RBM45 on its downstream genes. And the results revealed that RBM45 mediated the stabilization of BCL2 and Twist1 mRNA via respectively binding to their 3`UTR. Further assay results suggested RBM45 promoted HCC growth and metastasis upon BCL2 and Twist1. In short, we unveiled a novel role of RBM45 in promoting hepatocarcinogenesis via the post-transcriptional regulation of BCL2 and Twist1 expression. The results proposes that RBM45 may serve as a potential therapeutic target for HCC.
Keywords
RNA-binding protein, RBM45, BCL2, Twist1, HCC
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This is a list of supplementary files associated with this preprint. Click to download.
- RBM45TableS1..docx
- S1.jpg
RBM45 promoted THLE-2 cells proliferation, migration and invasion. A. RBM45 expression was significantly increased following the transfection of overexpression RBM45 vector into THLE-2 cells. B. MTT assay showed that RBM45 overexpression promoted THLE-2 cells proliferation. C. Overexpression of RBM45 reduced THLE-2 cells apoptosis. D. Transwell assays. The invaded cells were quantified by counting the cells in 10 random fields (magnification 200×). *p<0.05, **p<0.01.
- S2.jpg
BCL2 is an essential downstream effector of RBM45 on promoting HCC cells migration and invasion. A. B. Overexpression of BCL2 rescued the function of RBM45 altering HCC cells migration and invasion. C. D. Co-knockdown of BCL2 and Twist1 instead of single knockdown of BCL2 rescued the effect of increased RBM45 on HCC cell migration and invasion ability. *p<0.05, **p<0.01.
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Lili Han
Xi'an Jiaotong University Second Affiliated Hospital Department of Oncology
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4964-140X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 10 Jun, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The post-transcriptional of mRNA expression involved in the hepatocellular carcinoma (HCC) pathogenesis and progression need to be further explored. RBPs, the main undertaker of post-transcriptional regulatory process, has been shown to impact HCC carcinogenesis and progression. However, the role of RBP, RNA-binding motif 45 (RBM45) in hepatocarcinogenesis and its interaction with its potential target mRNA remains entirely unknown. The expression of RBM45 was significantly increased in HCC and was associated with poor clinicopathological features and clinical outcome of HCC patients. RBM45 promoted HCC cells growth, invasion, migration and EMT in vitro and in vivo. Mechanistically, RNA immunoprecipitation sequencing (RIP-seq) approach was utilized to screen the important differentially expressed RBM45 genes in HCC. Furthermore, RIP assay, pull-down assay and mRNA decay assay were carried out to uncover the effect of RBM45 on its downstream genes. And the results revealed that RBM45 mediated the stabilization of BCL2 and Twist1 mRNA via respectively binding to their 3`UTR. Further assay results suggested RBM45 promoted HCC growth and metastasis upon BCL2 and Twist1. In short, we unveiled a novel role of RBM45 in promoting hepatocarcinogenesis via the post-transcriptional regulation of BCL2 and Twist1 expression. The results proposes that RBM45 may serve as a potential therapeutic target for HCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
- RBM45TableS1..docx
- S1.jpg
RBM45 promoted THLE-2 cells proliferation, migration and invasion. A. RBM45 expression was significantly increased following the transfection of overexpression RBM45 vector into THLE-2 cells. B. MTT assay showed that RBM45 overexpression promoted THLE-2 cells proliferation. C. Overexpression of RBM45 reduced THLE-2 cells apoptosis. D. Transwell assays. The invaded cells were quantified by counting the cells in 10 random fields (magnification 200×). *p<0.05, **p<0.01.
- S2.jpg
BCL2 is an essential downstream effector of RBM45 on promoting HCC cells migration and invasion. A. B. Overexpression of BCL2 rescued the function of RBM45 altering HCC cells migration and invasion. C. D. Co-knockdown of BCL2 and Twist1 instead of single knockdown of BCL2 rescued the effect of increased RBM45 on HCC cell migration and invasion ability. *p<0.05, **p<0.01.
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