Is the regulation by miRNAs of NTPDase1 and ecto-5’-nucleotidase genes involved with the different profiles of breast cancer subtypes?

• Published in: Purinergic signalling Vol. 18; no. 1; pp. 123 - 133
• Main Authors: da Silva, Fernanda Cardoso, de Melo Neto, Angelo Borges, Martins, Christina Aparecida, de Sousa Cardoso, Thaís Cunha, de Souza Gomes, Matheus, de Araújo, Thaise Gonçalves, Fürstenau, Cristina Ribas
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-03-2022; Springer Nature B.V
• Subjects: 5'-Nucleotidase - genetics; 5'-Nucleotidase - metabolism; Antigens, CD; Apyrase; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer Research; CD39 antigen; Cell Line, Tumor; Epigenetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Gene regulation; Human Physiology; Humans; Hydrolysis; MicroRNAs - genetics; Neurosciences; Nucleotidase; Original; Original Article; Pharmacology/Toxicology; Post-transcription; Public health; Therapeutic targets; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; Tumors; CD73; Adenosine; Breast cancer; miR-141-3p; miR-101-3p; miR340-5p
• DOI: 10.1007/s11302-021-09824-4
• EISSN: 1573-9546
• ISSN: 1573-9538

Breast cancer (BC) is a public health problem worldwide, causing suffering and premature death among women. As a heterogeneous disease, BC-specific diagnosis and treatment are challenging. Ectonucleotidases are related to tumor development and their expression may vary among BC. miRNAs may participate in epigenetic events and may regulate ectonucleotidases in BC. This study aimed to evaluate the expression of ectonucleotidases according to BC subtypes and to predict if there is post-transcriptional regulation of them by miRNAs. MCF 10A (non-tumorigenic), MCF7 (luminal BC), and MDA-MB-231 (triple-negative BC - TNBC) breast cell lines were used and
ENTPD1
(the gene encoding for NTPDase1) and
NT5E
(the gene encoding for ecto-5’-nucleotidase) gene expression was determined. Interestingly, the expression of
ENTPD1
was only observed in MCF7 and
NT5E
was lower in MCF7 compared to MDA-MB-231 cell line. ATP, ADP, and AMP hydrolysis were observed on the surface of all cell lines, being higher in MDA-MB-231. Like qPCR, the activity of AMP hydrolysis was also lower in the MCF7 cells, which may represent a striking feature of this BC subtype. In silico analyses confirmed that the miRNAs miR-101-3p, miR-141-3p, and miR-340-5p were higher expressed in MCF7 cells and targeted
NT5E
mRNA. Altogether, data suggest that the regulation of
NT5E
by miRNAs in MCF7 lineage may direct the molecular profile of luminal BC. Thus, we suggest that the roles of ecto-5’-nucleotidase and the aforementioned miRNAs must be unraveled in TNBC to be possibly defined as diagnostic and therapeutic targets.