Abstract
Transcribed-ultraconserved regions (T-UCRs) are long non-coding RNAs (lncRNA) encoded by a subset of long ultraconserved stretches in the human genome. Recent studies revealed that the expression of several T-UCRs is altered in cancer and growing evidences underline the importance of T-UCRs in oncogenesis, offering also potential new strategies for diagnosis and prognosis. We found that overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients. uc.63 is localized in the third intron of exportin-1 gene (XPO1) and is transcribed in the same orientation of its host gene. Interestingly, silencing of uc.63 induces apoptosis in vitro. However, silencing of host gene XPO1 does not cause the same effect suggesting that the transcription of uc.63 is independent of XPO1. Our results reveal an important role of uc.63 in promoting breast cancer cells survival and offer the prospect to identify a signature associated with poor prognosis.
Highlights
Breast cancer is the most common tumor and the second leading cause of cancer deaths in women with over 1,400,000 new cases diagnosed every year worldwide
We found that overexpression of one specific Transcribed-ultraconserved regions (T-ultraconserved regions (UCRs)) named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients. uc.63 is localized in the third intron of exportin-1 gene (XPO1) and is transcribed in the same orientation of its host gene
Long non-coding RNA uc.63 overexpression is associated with poor prognosis in breast cancer uc.63 ultraconserved region (278bp) is localized on the chromosome 2p15, in the third intron of XPO1 gene (Exportin-1, CRM1) (Figure 1A)
Summary
Breast cancer is the most common tumor and the second leading cause of cancer deaths in women with over 1,400,000 new cases diagnosed every year worldwide. From the clinical point of view, breast cancer is characterized by wide heterogeneity. As well as immuno-histochemical analysis of estrogen receptor (ER) α, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) can classify human breast cancers in four major histopatological/therapeutical subtypes: luminal A, luminal B, HER2 and basal-like [1, 2]. HER2 group includes patients responsive to trastuzumab therapy, which has led to a great clinical success [3]. Known as triplenegative breast cancers, are characterized by the lack of expression ER, PR and HER2 [3]. This phenotype makes basal tumors difficult to treat, more aggressive and with poor prognosis compared to the other subtypes [4]
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