The long noncoding RNA sONE represses triple‐negative breast cancer aggressiveness through inducing the expression of miR‐34a, miR‐15a, miR‐16, and let‐7a

Abstract

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype. Among young females, TNBC is the leading cause of cancer-related mortalities. Recently, long noncoding RNAs (lncRNAs) are representing a promising pool of regulators for tuning the aggressiveness of several solid malignancies. However, this still needs further investigations in TNBC. The main aim of this study is to unravel the expression pattern of sONE lncRNA and its mechanistic role in TNBC. Results showed that sONE is restrictedly expressed in TNBC patients; its expression level is inversely correlated with the aggressiveness of the disease. sONE acts as a posttranscriptional regulator to endothelial nitric oxide synthase (eNOS) and thus affecting eNOS-induced nitric oxide (NO) production from TNBC cells measured by Greiss reagent. Mechanistically, sONE is a potential tumor suppressor lncRNA in TNBC cells; repressing cellular viability, proliferation, colony-forming ability, migration, and invasion capacities of MDA-MB-231. Furthermore, sONE effects were found to be extended to affect the maestro tumor suppressor TP53 and the oncogenic transcription factor c-Myc. Knocking down of sONE resulted in a marked decrease in TP53 and increase in c-Myc and consequently altering the expression status of their downstream tumor suppressor microRNAs (miRNAs) such as miR-34a, miR-15, miR-16, and let-7a. In conclusion, this study highlights sONE as a downregulated tumor suppressor lncRNA in TNBC cells acting through repressing eNOSinduced NO production, affecting TP53 and c-Myc proteins levels and finally altering the levels of a panel of tumor suppressor miRNAs downstream TP53/c-Myc proteins. K E Y W O R D S eNOS, long noncoding RNAs, microRNAs, nitric oxide, sONE, triple-negative breast cancer SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Youness RA, Hafez HM, Khallaf E, Assal RA, Abdel Motaal A, Gad MZ. The long noncoding RNA sONE represses triple-negative breast cancer aggressiveness through inducing the expression of miR-34a, miR-15a, miR-16, and let-7a.

Targeting hydrogen sulphide signaling in breast cancer

“…The trans-well migrant cells were fixed and stained using 1% crystal violet (Sigma Chemical Co., California, USA) and then counted under an inverted light microscope. All experiments were performed in triplicate and repeated 3 times or more [6] , [14] , [27] .…”

“…In cancer, we and others have recently reported that H 2 S acts as a key player in modulating several canonical and non-canonical oncogenic signaling pathways such as PI3K/AKT/mTOR [11] , JAK/STAT [12] , [13] , Ras/Raf/MEK/ERK [11] , and nitric oxide (NO) [14] signaling cascades. Our group also highlighted the regulatory effects of H 2 S on the non-coding RNA (ncRNA) machinery in BC cells [14] , [15] .…”

“…Human epidermal growth factor receptor 2 (HER2) positive tumors are amenable for treatment using HER2 targeting antibodies and HER2 specific tyrosine kinase inhibitors [3] . For triple negative breast cancer (TNBC), targeted treatment options are limited and outcomes have been substantially worse [4] , [5] , [6] . Collectively , this underscores BC, and particularly TNBC, as a significant worldwide problem in dire need for more efficacious and innovative therapies [7] , [8] .…”

Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

“…In contrast, several lncRNAs also play tumour suppressor roles in TNBC progression. Downregulating lncRNA SONE resulted in a remarkable TP53 decrease and c‐MYC increase, which could alter the expression of downstream tumour suppressor miRNAs, leading to increased cell proliferation and migration 97 . LncRNA RMST functioned as a tumour suppressor in TNBC by decreasing cell proliferation and migration, modulating the cell cycle and enhancing apoptosis 98 .…”

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

“…Rapidly developing transcriptomics analysis technology in recent years has revealed the potential regulatory mechanisms of lncRNAs in various diseases, especially in tumours [6,7]. lncRNAs can affect the proliferation and metastasis of cells by regulating gene promoter activity by sponging specific miRNAs, which are important factors in tumourigenesis [8,9]. Accumulating evidence supports that lncRNAs and miRNAs make up a regulatory network.…”