Regulation of MYO18B mRNA by a network of C19MC miRNA-520G, IFN-γ, CEBPB, p53 and bFGF in hepatocellular carcinoma

Goodwin G Jinesh; Marco Napoli; Hayley D Ackerman; Payal M Raulji; Nicole Montey; Elsa R Flores; Andrew S Brohl

doi:10.1038/s41598-020-69179-5

Regulation of MYO18B mRNA by a network of C19MC miRNA-520G, IFN-γ, CEBPB, p53 and bFGF in hepatocellular carcinoma

Sci Rep. 2020 Jul 23;10(1):12371. doi: 10.1038/s41598-020-69179-5.

Authors

Goodwin G Jinesh^{1

2}, Marco Napoli^{3

4}, Hayley D Ackerman^{3

4}, Payal M Raulji^{3

4}, Nicole Montey^{3

4}, Elsa R Flores^{3

4}, Andrew S Brohl^{5

6}

Affiliations

¹ Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. [email protected].
² Sarcoma Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. [email protected].
³ Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
⁴ Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
⁵ Sarcoma Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. [email protected].
⁶ Chemical Biology and Molecular Medicine Program. 12902 USF Magnolia Drive, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA. [email protected].

Abstract

MYO18B has been proposed to contribute to the progression of hepatocellular carcinoma (HCC). However, the signals that govern MYO18B transcription are not known. Here we show that, a network of C19MC miRNA-520G, IFN-γ, CEBPB and p53 transcriptional-defects promote MYO18B mRNA expression in HCCs. IFN-γ by itself suppresses MYO18B transcription, but promotes it when miRNA-520G is stably overexpressed. Similarly, CEBPB-liver-enriched activator protein (LAP) isoform overexpression suppresses MYO18B transcription but promotes transcription when the cells are treated with IFN-γ. Furthermore, miR-520G together with mutant-p53 promotes MYO18B transcription. Conversely, bFGF suppresses MYO18B mRNA irrespective of CEBPB, miR-520G overexpression or IFN-γ treatment. Finally high MYO18B expression reflects poor prognosis while high MYL5 or MYO1B expression reflects better survival of HCC patients. Thus, we identified a network of positive and negative regulators of MYO18B mRNA expression which reflects the survival of HCC patients.

MeSH terms

CCAAT-Enhancer-Binding Protein-beta / biosynthesis*
CCAAT-Enhancer-Binding Protein-beta / genetics
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / pathology
Cell Line
Female
Fibroblast Growth Factor 2 / biosynthesis*
Fibroblast Growth Factor 2 / genetics
Gene Expression Regulation, Neoplastic*
Humans
Interferon-gamma / biosynthesis*
Interferon-gamma / genetics
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology
Male
MicroRNAs / biosynthesis*
MicroRNAs / genetics
Myosins / biosynthesis*
Myosins / genetics
RNA, Messenger / biosynthesis*
RNA, Messenger / genetics
RNA, Neoplasm / biosynthesis*
RNA, Neoplasm / genetics
Tumor Suppressor Protein p53 / biosynthesis*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Proteins / biosynthesis*
Tumor Suppressor Proteins / genetics

Substances

CCAAT-Enhancer-Binding Protein-beta
CEBPB protein, human
IFNG protein, human
MIRN520 microRNA, human
MYO18B protein, human
MicroRNAs
RNA, Messenger
RNA, Neoplasm
TP53 protein, human
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
Fibroblast Growth Factor 2
Interferon-gamma
Myosins

Grants and funding

R35 CA197452/CA/NCI NIH HHS/United States