miR-145 promotes miR-133b expression through c-myc and DNMT3A-mediated methylation in ovarian cancer cells.

Abstract

Ovarian cancer presents as malignant tumors in the female reproductive system with high mortality. MicroRNAs are involved in the progression of ovarian cancer; however, the regulatory relationship among miRs remains unclear. In our study, we verified that both miR-145 and miR-133b messenger RNA (mRNA) levels in ovarian cancer tissues were lower than in normal ovarian tissues, and their mRNA level in serum of patients with ovarian cancer was reduced. We demonstrated miR-145 targeted c-myc, and c-myc interacted physically with DNMT3A in ovarian cancer cells. We confirmed that c-myc recruited DNMT3A to the miR-133b promoter. miR-133b overexpression also inhibited target gene PKM2 expression along with the Warburg effect. Our results indicate that miR-145 inhibited the Warburg effect through miR-133b/PKM2 pathways, which may improve approaches to ovarian cancer diagnosis and treatment.

• Authors: Jie Li, Songlin Zhang, Yuliang Zou, Lei Wu, Meili Pei, Yu Jiang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 235 Issue 5 Pg. 4291-4301 (05 2020) ISSN: 1097-4652 [Electronic] United States
• PMID: 31612498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Carrier Proteins
• DNMT3A protein, human
• Dnmt3a protein, mouse
• MIRN133 microRNA, human
• MIRN145 microRNA, human
• MYC protein, human
• Membrane Proteins
• MicroRNAs
• Proto-Oncogene Proteins c-myc
• Thyroid Hormones
• DNA (Cytosine-5-)-Methyltransferases
• DNA Methyltransferase 3A

Topics

• Animals
• Carrier Proteins (genetics, metabolism)
• Cells, Cultured
• DNA (Cytosine-5-)-Methyltransferases (genetics, metabolism)
• DNA Methylation
• DNA Methyltransferase 3A
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasms, Experimental (genetics, metabolism)
• Ovarian Neoplasms (metabolism)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Thyroid Hormones (genetics, metabolism)
• Thyroid Hormone-Binding Proteins