Suppressing the molecular signaling pathways involved in inflammation and cancer in breast cancer cell lines MDA-MB-231 and MCF-7 by miR-590

Abstract

Breast cancer is the most frequent cancer among women worldwide. Tumor immunology suggests relationships between the immune system, chronic inflammation, and cancer. The immune system may either prevent or promote carcinogenesis. Here, we evaluated molecular signaling pathways common in inflammation and cancer and detected the microRNAs which play pivotal roles in mediating these pathways. Using bioinformatics assays, signaling pathways common in inflammation and cancer, and microRNAs mediating these pathways were identified. MiR-590 was selected and cloned into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines. The expression level of microRNA and the candidate genes was evaluated by real-time quantitative reverse transcription polymerase chain reaction, and the apoptosis level in transfected cells was measured by Annexin V-7AAD assay. The cell migration was tested by real-time quantitative reverse transcription polymerase chain reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72 h after transfection. While miR-590 showed an over-expression, the genes were significantly down-regulated. A significant increase was observed in apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down-regulates critical genes of signaling pathways similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast cancer cell lines. Apparently, some microRNAs can be good candidates for novel treatments of cancer. Although miR-590 showed good results in this study, further studies are required to investigate the role of miR-590 in breast cancer therapy.

HHV-6A/6B Infection of NK Cells Modulates the Expression of miRNAs and Transcription Factors Potentially Associated to Impaired NK Activity

“…The up-regulated miR-101 and miR-381 are involved in the polarization and activation of the cells of the innate immune compartment, regulating the inflammatory response ( Zhu et al, 2010 ; Essandoh et al, 2016 ; Wen et al, 2016 ); the increased miR-548 may represent a mechanism facilitating viral pathogenesis as it negatively correlates with IFNγR1 levels ( Xing et al, 2014 ). miR-21 and miR-590, up-regulated by HHV-6A, are involved in differentiation and activation of T cells, particularly during autoimmunity ( Sousa et al, 2017 ), with miR-590 also down-regulating critical genes of signaling pathways similar in cancer and inflammation ( Sheikholeslami et al, 2017 ). miR-29 and miR-15, both increased by HHV-6A infection, have a specific role in regulating the cytotoxic activity of NK cells, inhibiting the production of IFNγ by directly targeting the 3′ UTR of its mRNA ( Ma et al, 2011 ; Leong et al, 2014 ).…”

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

“…GOLPH3 activity was also linked to breast cancer proliferation in the activating transcription factor 3 (ATF3)-miR-590-3p pathway [78]. miRNA-590-3p regulates breast cancer cell apoptosis by controlling the expression of important regulators of tumor formation and progression, such as of JAK2, PI3K, MAPK1, and CREB [79]. ATF3 is a stress-inducible protein, associated with malignant transformation and breast cancer metastasis [80].…”

Estrogen receptor-α regulation of microRNA-590 targets FAM171A1—a modifier of breast cancer invasiveness

“…These subtle differences could be possibly attributed due to the differential signaling cascade initiating from estrogen receptor-alpha (ERα), PGR, and Her2. In this context, miR590-5p is reported to be high in ERα-positive MCF-7 cells as compared to ERα-negative MDA-MB231 cells 17 , while another report found no change in the levels of miR590-5p (also known as OncomiR, anti-anti-OncomiR) between ER+ and ER− breast cancer cells 18 . A previous report shows that the miR590-5p containing genomic region, along with its promoter, resides within the EIF4H gene 19 , is an intergenic miRNA 20 .…”