Understanding Stim-1 Regulatory Networks in Nasopharyngeal Cancer Using Functional, Transcriptomics, Proteomics, and in-silico Approaches

Abstract Objective Stromal-interaction molecule 1 (STIM-1) aberrant expression contributes significantly to cancer pathogenesis. The present work studied STIM-1 regulatory networks in nasopharyngeal cancer (NPC) models via functional, transcriptome, translational, and in-silico approaches. Methods STIM-1 knockdown models were established in Epstein–Barr virus (EBV) related NPC cells (C666-1) and non-EBV related NPC cells (HK-1) respectively using DsiRNA technology. At the functional level, STIM-1 knockdown showed that it could regulate NPC oncogenic state possibly via calcium and ROS activities, especially in EBV-related NPC models. STIM-1 knockdown could inhibit EBV-related-NPC cells efficiently as compared to non-EBV-NPC cells. Regulation at transcriptomic and translation was observed in four critical regulatory networks involving PI3K/Akt, cell cycle, calcium signaling, and apoptosis. Results The PI3K/AKt pathway was found to be affected by the STIM-1 network in NPC through the association of miR-375, miR-185-5p, miR 200a-3p, let-7b-5p, and miR-34a-5p. In silico work support these findings, where miR-200a-3p and miR-375 docking scores showed a high probability of binding with STIM-1 and Epstein–Barr virus nuclear antigen 1 (EBNA-1) networks. Conclusion This study also found that NPC stemness was affected by STIM-1 suppression. Further analysis suggested STIM-1 regulatory networks have a positive correlation with the EBV status in NPC pathogenesis. Further work on NPC clinical samples is needed to support this work, especially in understanding the therapeutic potential of STIM-1 in NPC.