Abstract
Accumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve in the tumorigenesis, progression and even lead to poor prognosis of various carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p (miR-93) levels were confirmed to be significantly upregulated in breast cancer clinical samples (n=36) and metastatic cell line (MDA-MB-231) compared with those in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A). Moreover, further research stated that the capability of migration, invasion and proliferation changed along with the altered expression of miR-106b and miR-93 in breast cancer. PTEN, the tumor-suppressor gene, was discovered to be reduced in breast cancer tissues or MDA-MB-231 cells with high levels of miR-106b and miR-93, which were inversely expressed in PTEN overexpression tissues or cells. Based on the investigation, miR-106b and miR-93 induced the migration, invasion and proliferation and simultaneously enhanced the activity of phosphatidylinositol-3 kinase (PI3K)/Akt pathway of MCF-7 cells, which could be blocked by upregulation of PTEN. Furthermore, suppression of PTEN reversed the function induced by anti-miR-106b and anti-miR-93 in MDA-MB-231 cells, indicating that PTEN was directly targeted by these miRNAs and acted as the potential therapeutic target for breast cancer therapy. In short, reductive PTEN mediated by miR-106b and miR-93 promoted cell progression through PI3K/Akt pathway in breast cancer.
Highlights
Breast cancer was currently the most prevalent cancer among women in developed countries.[1]
It functions in converting phosphatidylinositol-3,4, 5-triphosphate (PIP3) into a diphosphate product (PIP2), inducing the antagonism of the phosphatidylinositol-3 kinase (PI3K) pathway and subsequently restraining tumor progress such as cell growth, apoptosis, adhesion, migration and invasion.[12,13]
When miR-106b mimics or miR-93 mimics and PTEN were co-transfected into MCF-7 cells, we interestingly found the ability of migration and invasion was recovered compared with that in MCF-7 cells overexpressed just miR-106b or miR-93 (Figures 5a and b)
Summary
Breast cancer was currently the most prevalent cancer among women in developed countries.[1]. Increasing attention was paid to exploring underlying molecular markers correlated with recrudescence and metastasis for the early diagnosis This provided possible therapeutic targets for breast cancer. PTEN, known as phosphatase and tensin homolog located on chromosome 10, is widely acknowledged as one of the most frequently deleted or mutated genes in diverse human tumors. It functions in converting phosphatidylinositol-3,4, 5-triphosphate (PIP3) into a diphosphate product (PIP2), inducing the antagonism of the phosphatidylinositol-3 kinase (PI3K) pathway and subsequently restraining tumor progress such as cell growth, apoptosis, adhesion, migration and invasion.[12,13] Currently, PTEN is widely researched and has been demonstrated to suppress the development of various carcinomas. Our results imply that PTEN is the direct target of miR-106b and miR-93, whose cancer-promoting function can be reversed by upregulation of PTEN in breast cancer
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