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

Author:

Mydin Rabiatul Basria SMN1,Azlan Adam1,Gooderham Nigel J.2,Mohamed Nur Mazidah Haji Noor1,Okekpa Simon I.3,Moses Emmanuel Jairaj1,Amran Syazwani Itri4,Musa Muhammad Yusri5

Affiliation:

1. Universiti Sains Malaysia (USM)

2. Imperial College London

3. Ebonyi State University

4. University of Technology Malaysia

5. Pusat Perubatan Universiti Sains Malaysia Bertam (PPUSMB), Universiti Sains Malaysia

Abstract

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.

Publisher

Research Square Platform LLC

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