SARS-CoV-2 spike protein exerts an anti-cancer effect by regulating MEG3 and BCYRN1 in A549 cells

Methods

To evaluate its anticancer activity, we performed RNA sequencing, colony formation, immunofluorescence, cell viability, migration, FACS, western blotting, 3D spheroid, molecular docking, siRNA,qRT-PCR, and apoptosis assays. Results Spike protein significantly inhibited the long-term growth of A549 cells. Among the delivery methods, PSV showed the most potent anticancer effect, followed by SPT and SP, as evidenced by suppressed migration, spheroid growth, and sub-G1 arrest.

RNA-Seq revealed distinct expression profiles between control and SP-treated cells, identifying two differentially expressed lncRNAs: MEG3 was upregulated, while BCYRN1 was downregulated. Knockdown of BCYRN1 or overexpression of MEG3 reproduced the spike protein–induced antiproliferative and pro-apoptotic effects, including enhanced cleaved caspase-3 expression. Docking analysis suggested potential binding of spike protein to these lncRNAs.

To determine whether spike protein affects their stability, transcription was inhibited using actinomycin D (ActD). Spike protein attenuated the ActD-induced decrease of MEG3, indicating enhanced stability, whereas it accelerated BCYRN1 reduction. Conclusion Collectively, these findings demonstrate that SARS-CoV-2 spike protein exerts antitumor activity in A549 lung cancer cells by differentially regulating the stability of lncRNAs MEG3 and BCYRN1.