Abstract
Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role in the underlying regulatory mechanism in TNBC are lacking. In this study, we investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the m6A methylated RNA was dramatically decreased in TNBC tissues and cell lines. Functionally, we demonstrated that METTL3 inhibits the proliferation, migration, and invasion ability of TNBC cells. Moreover, we found METTL3 is repressed by miR-34c-3p in TNBC cells. On the mechanism, we found that circMETTL3 could act as a sponge for miR-34c-3p and inhibits cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR-34c-3p target gene METTL3. In conclusion, our study demonstrates the functional importance and regulatory mechanism of METTL3 in suppressing the tumor growth of TNBC.
Highlights
Breast cancer is the most common cancer among women
The evaluation of cell migration ability was performed by using wound scrape assay to examine the role of METTL3, miR-34c-3p and circMETTL3 in the regulation of migration ability of Triple negative breast cancer (TNBC) cell lines as described previously [33]
Expression of N6-Methyladenosine Methyltransferase METTL3 and m6A Level Is Decreased in TNBC Tissues and Cell Lines
Summary
Breast cancer is the most common cancer among women. According to Global Cancer Statistics, there were 2,088,849 new cases and 626,679 deaths from breast cancer worldwide in 2018, accounting for nearly a quarter of all cancer cases among women worldwide [1, 2]. MicroRNAs (miRNAs) are a class of small non-coding RNAs that are evolutionarily conserved and regulate gene expression at the post-transcriptional level through targeted mRNA, leading to mRNA degradation or translation inhibition. More and more evidence indicate that circRNAs may be involved in the progression of breast, stomach, colorectal, bladder and hepatocellular carcinoma as ceRNAs [26,27,28,29] It is unclear which circRNAs may regulated the level of METTL3 in the tumorigenesis and tumor progression of TNBC. We investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. Further studies showed that circMETTL3 could act as a sponge for miR-34c-3p and promote cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR34c-3p target gene METTL3. CircMETTL3 inhibits the tumor growth of triple negative breast cancer via miR-34c3p/METTL3 signaling
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