Open AccessDouble‐negative feedback interaction between DNA methyltransferase 3A and microRNA‐145 in the Warburg effect of ovarian cancer cells
Author(s) -
Zhang Songlin,
Pei Meili,
Li Zhen,
Li Han,
Liu Yanli,
Li Jie
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13734
Subject(s) - warburg effect , gene knockdown , dna methyltransferase , ovarian cancer , microrna , cancer research , biology , methylation , methyltransferase , downregulation and upregulation , microbiology and biotechnology , dna methylation , cancer , cancer cell , gene expression , cell culture , gene , genetics
Ovarian cancer is the most lethal gynecological malignancy because of its poor prognosis. The Warburg effect is one of the key mechanisms mediating cancer progression. Molecules targeting the Warburg effect are therefore of significant therapeutic value for the treatment of cancers. Many micro RNA s (miR) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with the Warburg effect in cancer cells. In our study, we found that miR‐145 negatively correlated with DNA methyltransferase ( DNMT )3A expression at cellular/histological levels. miR‐145 inhibited the Warburg effect by targeting HK 2. Luciferase reporter assays confirmed that miR‐145‐mediated downregulation of DNMT 3A occurred through direct targeting of its mRNA 3′‐ UTR s, whereas methylation‐specific PCR ( MSP ) assays found that knockdown of DNMT 3A increased mRNA level of miR‐145 and decreased methylation levels of promoter regions in the miR‐145 precursor gene, thus suggesting a crucial crosstalk between miR‐145 and DNMT 3A by a double‐negative feedback loop. DNMT 3A promoted the Warburg effect through miR‐145. Coimmunoprecipitation assays confirmed no direct binding between DNMT 3A and HK 2. In conclusion, a feedback loop between miR‐145 and DNMT 3A is a potent signature for the Warburg effect in ovarian cancer, promising a potential target for improved anticancer treatment.