Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1), a lncRNA that was first recognized as a prognostic parameter for patient survival of stage I lung cancer, is up-regulated in multiple human malignancies, including breast cancer. However, the mechanism of its function remained elusive. In the current study, by examining MALAT1 expression on mRNA level, we demonstrated that compared with MCF10A, MALAT1 expression was up-regulated in the majority of breast cancer cell lines (9/12). In 26 pairs of estrogen receptor (ER)-positive breast cancer samples, MALAT1 expression was significantly up-regulated compared with adjacent normal tissues (P = 0.012). Furthermore, of 204 breast cancer patients, high MALAT1 expression was associated with positive ER (P = 0.023) and progesterone receptor (PR) (P = 0.024) status. Further analysis using TCGA database revealed that ER and its target genes PGR and CCND1, were overexpressed in MALAT1 altered group compared with unaltered group, both on the mRNA and protein level. Lastly, we verified MALAT1's prognostic value in breast cancer. At the cut-off value of 75%, MALAT1 was the only independent prognostic factor of recurrence-free survival (RFS) in ER-negative patients in a multivariate Cox regression model (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.02–7.83). MALAT1 overexpression was also associated with poor RFS in tamoxifen treated ER-positive breast cancer patients, which might serve as a potential biomarker to predict endocrine treatment sensitivity.
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs in the human genome that involves in breast cancer development and progression. Here, we identify a lncRNA, LINC00978, which is upregulated in breast cancer cell lines and tissues compared with corresponding controls. Furthermore, LINC00978 expression is negatively associated with hormone receptor (HR) status in 195 breast cancer patients studied (p = 0.033). Kaplan–Meier survival analysis shows that patients with high LINC00978 expression have poorer disease-free survival (DFS) than those with low LINC00978 expression (p = 0.012), and multivariate analysis identifies LINC00978 as an independent prognostic factor in breast cancer (p = 0.008, hazard ratio [HR] = 2.270, 95% confidence interval [CI] 1.237–4.165). Our study indicates that LINC00978 may be an oncogene in breast cancer, and can serve as a potential biomarker to predict prognosis in breast cancer patients.
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