Arsenic trioxide-induced upregulation of miR-1294 suppresses tumor growth in hepatocellular carcinoma by targeting TEAD1 and PIM1.

Abstract

Recently, Arsenic trioxide (ATO) has been reported as an efficient drug for suppression of cancer cell growth. Existing studies revealed the extensive involvement of microRNAs (miRNAs) in initiation and development of hepatocellular carcinoma (HCC). However, the potential correlation between ATO and miRNAs in HCC progression remains to be explored. To conduct our research, we applied a qRT-PCR analysis to find miRNAs that were upregulated in HCC cells treated with ATO. In our present study, miR-1294 was found to be significantly upregulated in ATO-treated HCC cells. To confirm the function of ATO and miR-1294 in HCC progression, gain-of function assays were designed and conducted. As expected, proliferative ability of ATO-treated HCC cells was markedly weakened compared to DMSO-treated HCC cells. More importantly, proliferation was further suppressed in ATO-induced HCC cells after overexpression of miR-1294. Through bioinformatics analysis, some potential targets of miR-1294 were predicted. Further investigation revealed that Pim-1 proto-oncogene (PIM1) and TEA domain transcription factor 1 (TEAD1) were two downstream targets of miR-1294 and could be negatively regulated by ATO. Functionally, we determined that cell proliferation and apoptosis resistance suppressed by miR-1294 and ATO were recovered by introduction of TEAD1 and PIM1. Collectively, this study revealed that a novel ATO-miR-1294-TEAD1/PIM1 axis regulated HCC cell growth, offering a potential insight into the HCC therapy.

• Authors: Xiaoniao Cai, Leilei Yu, Zhen Chen, Fangpeng Ye, Zonghai Ren, Peisheng Jin
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 28 Issue 2 Pg. 221-230 ( 2020) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 32280078 (Publication Type: Journal Article)

Chemical References

• DNA-Binding Proteins
• MAS1 protein, human
• MIRN1294 microRNA, human
• MicroRNAs
• Nuclear Proteins
• Proto-Oncogene Mas
• TEA Domain Transcription Factors
• TEAD1 protein, human
• Transcription Factors
• PIM1 protein, human
• Proto-Oncogene Proteins c-pim-1
• Arsenic Trioxide

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Arsenic Trioxide (pharmacology, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Computational Biology
• DNA-Binding Proteins (genetics)
• Female
• Gain of Function Mutation
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (drug therapy, genetics, pathology)
• Mice
• MicroRNAs (genetics, metabolism)
• Nuclear Proteins (genetics)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-pim-1 (genetics)
• TEA Domain Transcription Factors
• Transcription Factors (genetics)
• Up-Regulation (drug effects)
• Xenograft Model Antitumor Assays