Sp1-mediated ectopic expression of T-cell lymphoma invasion and metastasis 2 in hepatocellular carcinoma

Cancer Medicine
Wei-Hsuan YenH S Sun

Abstract

T-cell lymphoma invasion and metastasis 2 (TIAM2) is a neuron-specific protein that has been found ectopically expressed in hepatocellular carcinoma (HCC). Results from clinical specimens and cellular and animal models have shown that the short form of TIAM2 (TIAM2S) functions as an oncogene in the tumorigenesis of liver cancer. However, the regulation of TIAM2S ectopic expression in HCC cells remains largely unknown. This study aimed to identify the mechanism underlying the ectopic expression of TIAM2S in liver cancer cells. In this report, we provide evidence illustrating that Sp1 binds directly to the GC box located in the TIAM2S core promoter. We further demonstrated that overexpression of Sp1 in HepaRG cells promotes endogenous TIAM2S mRNA and protein expressions, and knockdown of Sp1 in 2 HCC cell lines, HepG2 and PLC/PRF/5, led to a substantial reduction in TIAM2S mRNA and protein in these cells. Of 60 paired HCC samples, 70% showed a significant increase (from 1.1- to 3.6-fold) in Sp1 protein expression in the tumor cells. The elevated Sp1 expression was highly correlated with both TIAM2S mRNA and protein expressions in these samples. Together, these results illustrate that Sp1 positively controls TIAM2S transcription a...Continue Reading

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Citations

May 20, 2020·Nucleic Acids Research·Giuseppa GrassoRosemary Kiernan
Jun 18, 2019·Therapeutic Advances in Medical Oncology·Yanzhi JiangDamu Tang
Nov 30, 2018·Cell Proliferation·Rong WangYongqian Shu

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Datasets Mentioned

BETA
Z11168.1

Methods Mentioned

BETA
sumoylation
glycosylation
electrophoretic mobility shift assay
immunoprecipitation
PCR
ChIP
transfection
reverse transcription PCR

Software Mentioned

GraphPad
GraphPad Prism

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