Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors

Cancer Science
Yasuo TakashimaAtsushi Suzuki

Abstract

Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer cases and has an extremely poor prognosis. Therefore, novel innovative therapies for HCC are strongly desired. As gene therapy tools for HCC, 2 hepatic transcription factors (TF), HNF4A and HNF1A, have been used to suppress proliferation and to extinguish cancer-specific characteristics of target cells. However, our present data demonstrated that single transduction of HNF4A or HNF1A had only a limited effect on suppression of HCC cell proliferation. Thus, in this study, we examined whether combinations of TF could show more effective antitumor activity, and found that combinatorial transduction of 3 hepatic TF, HNF4A, HNF1A and FOXA3, suppressed HCC cell proliferation more stably than single transduction of these TF. The combinatorial transduction also suppressed cancer-specific phenotypes, such as anchorage-independent growth in culture and tumorigenicity after transplantation into mice. HCC cell lines transduced with the 3 TF did not recover their proliferative property after withdrawal of anticancer drugs, indicating that combinatorial expression of the 3 TF suppressed the growth of all cell subtypes within the HCC cell lines, including cancer st...Continue Reading

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Citations

Dec 22, 2019·International Journal of Molecular Sciences·Jorge SimonMaría Luz Martínez-Chantar
Mar 11, 2020·International Journal of Molecular Sciences·Raynoo ThananChawalit Pairojkul
May 23, 2020·Scientific Reports·Yasuo TakashimaRyuya Yamanaka
Apr 6, 2021·Current Hepatology Reports·Adeniji Nia, Renumathy Dhanasekaran

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Datasets Mentioned

BETA
GSE18269
GSE115423

Methods Mentioned

BETA
Assay
xenografts
PCR

Software Mentioned

Bowtie2
Amira
GSEAPreranked
Cufflinks
TopHat2
Database for Annotation , Visualization , and Integrated Disco...
GEO2R
JMPv10
GSEA

Related Concepts