miR-770-5p regulates EMT and invasion in TNBC cells by targeting DNMT3A

Noyan, Senem
Andaç Özketen, Ayşe
Gurdal, Hakan
Gur Dedeoglu, Bala
MicroRNAs (miRNAs) are shown to regulate various processes in cancer like motility and invasion that are key features of the metastatic triple negative breast cancer (TNBCs). Epithelial-mesenchymal transition (EMT) is one of the well-defined cellular transitioning processes characterized with reduced E-cadherin expression and increased mesenchymal molecules such as Vimentin or Snail thereby gives the cells mobility and invasive character. Aberrant DNA methylation by DNA methyltransferases (DNMTs) plays an important role in carcinogenesis. It is well known that DNMTs are required for transcriptional silencing of tumor-associated genes. DNMT3A-induced promoter hypermethylation of E-cadherin has also been known to improve cancer metastasis. Our results indicated that miR-770-5p could downregulate Vimentin and Snail expression levels, while increasing or restoring the expression of E-Cadherin hence, leading to inhibition of EMT phenotypes along with motility and invasion. Specifically, we showed that overexpression of miR-770-5p restored the expression of E-Cadherin in MDA-MB-231 cells via directly targeting DNMT3A. We also observed the change in the spindled shapes showing the loss of mesenchymal characteristics and gain of epithelial phenotype in miR-770-5p overexpressing cells. When considered together, our results show that miR-770-5p could effectively inhibit invasion potential driven by EMT.
Cellular Signalling


GST isoenzymes in matched normal and neoplastic breast tissue
OĞUZTÜZÜN, SERPİL; Abu-Hijleh, A.; ÇOBAN, TÜLAY; Bulbul, D.; KILIÇ, MURAT; İŞCAN, Mümtaz; İşcan, Mesude (AEPress, s.r.o., 2011-01-01)
The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression.
Targeting HIF1-alpha/miR-326/ITGA5 axis potentiates chemotherapy response in triple-negative breast cancer
Assidicky, Ridho; Tokat, Unal Metin; Tarman, Ibrahim Oguzhan; Saatci, Ozge; Ersan, Pelin Gulizar; Raza, Umar; Ogul, Hasan; Riazalhosseini, Yasser; Can, Tolga; Sahin, Ozgur (2022-03-01)
Purpose Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that is frequently treated with chemotherapy. However, many patients exhibit either de novo chemoresistance or ultimately develop resistance to chemotherapy, leading to significantly high mortality rates. Therefore, increasing the efficacy of chemotherapy has potential to improve patient outcomes. Methods Here, we performed whole transcriptome sequencing (both RNA and small RNA-sequencing), coupled with network simu...
MTA-1 expression is associated with metastasis and epithelial to mesenchymal transition in colorectal cancer cells
Cagatay, Seda Tuncay; Cimen, Ismail; SAVAŞ, BERNA; Banerjee, Sreeparna (Springer Science and Business Media LLC, 2013-04-01)
Although metastasis associated protein 1 (MTA1) has been widely linked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in colorectal cancer (CRC). Here, we have investigated the link between MTA1, metastasis and epithelial-mesenchymal transition (EMT) in CRC. Eighteen normal colon tissues and 91 resected tumor samples were analyzed for MTA1 expression by immunohistochemistry (IHC). IHC indicated low or no nuclear MTA1 expression in the normal tissues and significantly higher...
Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer
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Aldo-keto reductases (including AKR1B1 and AKR1B10) constitute a family of oxidoreductases that have been implicated in the pathophysiology of diabetes and cancer, including colorectal cancer (CRC). Available data indicate that, despite their similarities in structure and enzymatic functions, their roles in CRC may be divergent. Here, we aimed to determine the expression and functional implications of AKR1B1 and AKR1B10 in CRC.
Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity
Simoes, Bruno M.; et. al. (2015-09-01)
Breast cancers (BCs) typically express estrogen receptors (ERs) but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC) activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX) tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen...
Citation Formats
S. Noyan, A. Andaç Özketen, H. Gurdal, and B. Gur Dedeoglu, “miR-770-5p regulates EMT and invasion in TNBC cells by targeting DNMT3A,” Cellular Signalling, pp. 0–0, 2021, Accessed: 00, 2021. [Online]. Available: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85103705276&origin=inward.