RGD Reference Report - SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma. - Rat Genome Database

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SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma.

Authors: Liu, Zhiyong  Li, Wei  Pang, Yanan  Zhou, Zaixin  Liu, Shupeng  Cheng, Kai  Qin, Qin  Jia, Yin  Liu, Shanrong 
Citation: Liu Z, etal., EBioMedicine. 2018 Dec;38:57-68. doi: 10.1016/j.ebiom.2018.10.067. Epub 2018 Nov 1.
RGD ID: 155804298
Pubmed: PMID:30391496   (View Abstract at PubMed)
PMCID: PMC6306498   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ebiom.2018.10.067   (Journal Full-text)


BACKGROUND: Splicing factor 3b subunit 4 (SF3B4) is a splicing factor and potential oncogene in hepatocellular carcinoma (HCC); however, its regulatory mechanism is yet unclear. We aimed to determine the role of SF3B4 in HCC and the underlying mechanism.
METHODS: To investigate the association between alternative splicing events and miRNAs, putative miRNAs were screened using TargetScan. Expression levels of and prognostic information for SF3B4 and miRNAs were determined based on public genomic data and clinical samples. Then, we examined the possible roles of SF3B4 and miRNA-133b in HCC cells and a xenograft mouse model. Pearson correlation analysis and in vitro experiments verified SF3B4 as a miRNA-133b target. Protein levels of key targets from the SF3B4 signaling pathway were estimated using western blotting.
FINDINGS: The expression of SF3B4 was upregulated in HCC tissues and cell lines whereas, the expression of miRNA-133b was downregulated. MiRNA-133b negatively regulated the expression of SF3B4. Effects of SF3B4 overexpression were partially abolished by miRNA-133b mimics, confirming that SF3B4 is a target of miRNA-133b. Moreover, molecules associated with SF3B4, including KLF4, KIP1, and SNAI2, were also modulated by miRNA-133b.
INTERPRETATION: SF3B4 plays a crucial role in HCC and is negatively regulated by miRNA-133b. The miRNA-133b/ SF3B4 axis may serve as a new therapeutic target for HCC treatment. FUND: China National Funds for Distinguished Young Scientists (No.81425019), the State Key Program of National Natural Science Foundation of China (No.81730076), Shanghai Science and Technology Committee Program (No.18XD1405300) and Specially-Appointed Professor Fund of Shanghai (GZ2015009). China National Funds for National Natural Science Fund (No.81672899).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma severityIEP 155804298mRNA:decreased expression:liver(human)RGD 
hepatocellular carcinoma severityISOMIR133B (Homo sapiens)155804298; 155804298mRNA:decreased expression:liver(human)RGD 
hepatocellular carcinoma severityIEP 155804298mRNA and protein:increased expression:liver(human)RGD 
hepatocellular carcinoma  IMP 155804298human cells in mouse modelRGD 
hepatocellular carcinoma severityISOSF3B4 (Homo sapiens)155804298; 155804298mRNA and protein:increased expression:liver(human)RGD 
hepatocellular carcinoma  ISOSF3B4 (Homo sapiens)155804298; 155804298human cells in mouse modelRGD 
lung metastasis  IMP 155804298human cells in mouse modelRGD 
lung metastasis  ISOSF3B4 (Homo sapiens)155804298; 155804298human cells in mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir133b  (microRNA 133b)
Sf3b4  (splicing factor 3B subunit 4)

Genes (Mus musculus)
Mir133b  (microRNA 133b)
Sf3b4  (splicing factor 3b, subunit 4)

Genes (Homo sapiens)
MIR133B  (microRNA 133b)
SF3B4  (splicing factor 3b subunit 4)


Additional Information