MicroRNA‑27a promotes tumorigenesis via targeting AKT in triple negative breast cancer

Abstract

Altered microRNA (miRNA/miR) expression regulates tumor development and progression in triple‑negative breast cancer (TNBC). The present study examined the effect of miR‑27a on proliferation, migration and invasion of TNBC cells in vitro and in vivo. An MTT assay was performed to examine the proliferation of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells with either overexpression of miR‑27a or downregulation of miR‑27a, in the presence or absence of radiation. The migratory and invasive abilities of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells were assessed by Transwell migration and Matrigel invasion assays. The protein expression levels were examined by western blotting. The caspase‑Glo3/7 assay was performed to examine the effect of miR‑27a on radiation‑induced apoptosis in MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells. A luciferase assay was performed to evaluate the effect of miR‑27a on phosphatase and tensin homolog (PTEN) and B cell lymphoma (Bcl)‑2 associated X, apoptosis regulator (BAX) expression. Immunodeficient nude mice were used to examine tumor growth following injection of MDA‑MB‑231 breast cancer cells. miR‑27a promoted proliferation in vitro and in vivo, and enhanced migration and invasion in TNBC cells. miR‑27a improved the survival of TNBC cells following irradiation. miR‑27a inhibited radiation‑induced apoptosis in TNBC cells by regulation of caspase 3/7 and Bcl‑2 expression. Furthermore, the expression levels of PTEN and phosphorylated protein kinase B in MDA‑MB‑231 and MDA‑MB‑468 cells was altered following overexpression of miR‑27a. The luciferase assay demonstrated that miR‑27a regulated PTEN and BAX expression by binding to 3'‑untranslated regions. Overall, miR‑27a exhibits an essential role in tumor development and progression in TNBC and may be used as a potential biomarker to predict radiotherapy response and prognosis for the disease.

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

“…4c). Conversely, the expression of PTEN, an inhibitor of PIK3/AKT signalling, increased in miR-27a_KD cells while diminished in miR-27a_OE cells with respect to their controls, consistent with PTEN being a direct target of miR-27a 40 (Fig. 4c).…”

“…In cancer cells, mTOR can be regulated by the mitogenresponsive signalling, such as PI3K/AKT which contributes to tumorigenesis and chemoresistance. 14,39,40 Interestingly, we found that AKT phosphorylation was reduced in HCT116 and SW480 miR-27a_KD cells while increased in HT29 miR-27_OE (Fig. 4c).…”

“…Since miR-27a overexpressing CRC cells proliferate more and have increased invasive and migratory potential ( Supplementary Fig. 2C-E), as in diverse cancer types, 26,40,45,50 they ought to upregulate several biosynthetic pathways (nucleotides, proteins, lipids) to favour biomass production and availability of ATP to sustain tumour growth. We show here that high-miR-27a expressing tumours (COAD) and cells manage these requirements by restricting catabolic pathways and diverting glycolytic intermediates to enhance the pentose phosphate pathway (PPP) ( Fig.…”

Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer

“…Comparison of the lists of highly expressed miRNAs identified in analyzed cells revealed seven molecules, whose oncogenic properties were already associated with this cancer type, that may represent a novel molecular biomarkers or therapeutic targets for treatment of this disease. Indeed, cell viability and epithelial-mesenchymal transition-promoting properties of miR-221-3p were already described, together with its ability to induce cell proliferation of TNBC cells [73], a characteristic feature known also for another four highly expressed miRNAs: miR-181b-5p, miR-21-3p, miR-25-3p, and miR-27a-3p [44,47,74,75]. Moreover, highly expressed miRNAs miR-103-3p, miR-181b-5p, miR-20a-5p, miR-21a-3p, miR-221-3p, and miR-27a-3p are involved in regulation of TNBC cells migration [44][45][46][73][74][75], whereas miR-103-3p, miR-20a-5p, and miR-27a-3p have been previously associated with invasion of TNBC cells [45,46,75].…”

“…Moreover, expression of miR-181b-5p represents a common feature of aggressive breast cancers [74], whereas another two miRNAs-miR-103-3p and miR-20a-5p-were found to be highly expressed in both TNBC tissues and cell lines [45,46]. Finally, it was demonstrated that overexpression of miR-27a-3p and miR-181b-5p confers chemoresistance to PARP (poly ADP ribose polymerase) inhibitors [39] and neutralizes the ionizing radiation effect [43,75], respectively. Altogether, these data indicate that the sncRNA expression dataset generated here represents a valuable source of information for further evaluation of potential of aforementioned miRNAs and other molecules as molecular biomarkers of TNBC.…”