Abstract
Pyridoxine 5′-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.
Highlights
Breast cancer is the most common malignant tumor and the second leading cause of cancer death in women worldwide [1]
PNPO is overexpressed in invasive ductal carcinoma (IDC) and correlated with clinicopathological features The expression of PNPO mRNA and protein was higher in breast IDC tissues than adjacent normal breast tissues and fibroadenomas tissues (Figure 1A and 1B)
The present study demonstrated for the first time that PNPO was upregulated in IDC at mRNA and protein levels and correlated with the overall survival of patients with breast cancer
Summary
Breast cancer is the most common malignant tumor and the second leading cause of cancer death in women worldwide [1]. Our previous study has shown that pyridoxine 5′-phosphate oxidase (PNP oxidase, PNPO) is overexpressed in human ovarian cancer and is a potential tumor progression marker [4]. PNPO activity affects PLP product and the biological behavior of ovarian cancer cells [4] and has an influence on colorectal cancer [8]. The biological function of PNPO in human breast IDC has not been studied yet. The correlation of PNPO expression with the breast cancer hormone therapyrelated markers such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) is not clear. A regulatory mechanism of PNPO is not fully understood
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