3'UTR of SARS-CoV-2 spike gene hijack host miR-296 or miR-520h to disturb cell proliferation and cytokine signaling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3'UTR of SARS-CoV-2 S (S-3'UTR) gene and bioinformatic predicted targeting miRNAs. The growth of 293T cells and HUVECs with overexpressed S-3'UTR was determined, while miRNAs and IL6, TNF-α levels were checked in this condition. Then, miR-296 and miR-602 mimic were introduced into 293T cells and HUVECs with overexpressed S-3'UTR, respectively, to reveal the underlying regulation mechanism. In results, we screened 19 miRNAs targeting the S-3'UTR, including miR-296 and miR-602. In 293T cell, S-3'UTR could inhibit 293T cell growth through down-regulation of miR-296. By reducing miR-602, S-3'UTR could induce HUVECs cell proliferation, alter the cell cycle, reduce apoptosis, and enhanced IL6 and TNF-αlevel. In conclusion, SARS-CoV-2 RNA could play as sponge of host miRNA to disturb cell growth and cytokine signaling. It suggests an important clue for designing COVID-19 drug and vaccine.