PO-347 sONE, a novel tumour suppressor lncRNA, with diminished expression level in young triple negative breast cancer (TNBC) patients with lymphnode metastasis and large tumour size

Abstract

IntroductionA recent surveillance of the human transcriptome has highlighted a pivotal class of RNA known as long non-coding RNA (lncRNAs). Myriad studies have reported the vital role of lncRNAs in oncology. However, the field is still in its infancy. lncRNAs are expressed in a highly cancer type-specific manner, thus could hold a lot of promises for personalised cancer therapy. In 2015, sONE has been identified as a novel lncRNA that acts as a post-transcriptional regulator of endothelial nitric oxide synthase (NOS3) expression in cultured endothelial cells. However, the role of sONE has never been investigated in any type of malignancy including Breast Cancer (BC). Among BC patients, TNBC is associated with the worst prognosis especially in young women (<40 years old). Young TNBC patients exhibit the most aggressive behaviour of tumours. Recently, few studies have been dedicated to identify actionable targets to this hard-to-treat group of patients. Therefore, our aim is to evaluate the expression pattern of sONE and its down-stream target (NOS3) in TNBC patients and to validate the role of sONE/NOS3/NO signalling cascade in TNBC cell linesMaterial and methodsBreast tissues were collected from 70 BC patients. Ki67 levels were quantified using immunohistochemistry. Clinical data of all patients were collected. MDA-MB-231 human BC cell lines were transfected using different oligonucleotides. Total RNA was extracted and quantified using qRT-PCR. NO production was assessed using Greiss reagent method. Cellular viability and proliferation were measured using MTT, BrdU assays, respectivelyResults and discussions sONE was significantly down-regulated in TNBC patients compared to its normal counterparts. Within TNBC patients, young females showed a diminished expression level of sONE. Furthermore, sONE expression pattern was inversely correlated with tumour size and lymph node metastasis in young TNBC patients. Our results showed that NOS3 expression level was reciprocally up-regulated.On the molecular level, sONE siRNAs resulted in an increase in NOS3 levels and NO production in MDA-MB-231. On the functional level, knocking down of sONE levels resulted in a significant increase of cellular viability and cellular proliferation rates of MDA-MB-231ConclusionThis study highlights a novel prognostic value of sONE in young TNBC patients where sONE expression level was negatively correlated with the aggressiveness of the disease. Moreover, this study validated sONE/NOS3/NO as a novel tumour suppressor signalling axis in BC patients.