4.7 Article

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

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 235, Issue 5, Pages 4291-4301

Publisher

WILEY
DOI: 10.1002/jcp.29306

Keywords

c-myc; DNMT3A; miR-133b; miR-145; ovarian cancer; Warburg effect

Funding

  1. Fundamental Research Funds for the Central Universities [XZY012019105]
  2. National Natural Science Foundation of China [81702577]
  3. Natural Science Basic Research Program of Shaanxi [2018JQ8035]

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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.

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