Breast cancer (BC) is one of the major biomedical research priorities worldwide. Luminal B and triple negative BC patients represents the worst prognosis and highest incidence of recurrence. Among those patients, metastasis is the missing piece in the puzzle. Consequently, extensive research is urgently required to identify specific molecular targets responsible for luminal B and TNBC induced risk of metastasis. ICAM-1 (known as CD54) and PVR (known as CD155) are transmembrane glycoproteins that have been emerged as novel molecular targets that are markedly up-regulated in BC patients. Our group is recently focusing on unraveling the role of Long non-coding RNAs in regulating vital molecular targets in BC patients. LncRNAs regulating ICAM-1 and PVR is still a virgin field. Therefore, the aim of this study is to identify a lncRNA that could dually target ICAM-1 and PVR simultaneously.
Forty BC patients were recruited. Bioinformatic analysis was performed to identify a lncRNA that could directly or indirectly target ICAM-1 and PVR. MDA-MB-231 and MCF-7 cells were cultured. Cells were transfected using Scrambled and H19 siRNAs by lipofection Technique. Total RNA was extracted using biozol from tissues and cell lines. Reverse transcription and qRT-PCR were performed. MTT, scratch and colony forming assays were performed. Student t-test was performed for statistical analysis.
In silico, H19 lncRNA was found to indirectly target ICAM-1 and PVR through STAT3 axis. H19, ICAM-1 and PVR were found to be upregulated in BC patients. Upon patients stratification, H19 and PVR were found to be specifically upregulated in luminal B BC patients while ICAM-1 was found to be specifically upregulated in TNBC patients. Upon Knocking down of H19, transfection effeciency was evaluated and H19 siRNAs resulted in paradoxical impacts on ICAM-1 and PVR. Yet, H19 siRNAs resulted in a repression of cellular viability, colonogenicity and migration capacity.
H19 inhibitory impact on the metastatic mediator ICAM-1 overrides its inductory effect on PVR in BC cells. Therefore, this study highlights H19 as an oncogenic lncRNA in BC and a novel molecular target for resistant luminal B and TNBC patients.
German University in Cairo.
Has not received any funding.
All authors have declared no conflicts of interest.