Epstein-Barr virus-encoded small non-coding RNAs induce cancer cell chemoresistance and migration

Epstein-Barr virus (EBV) encoded small, non-coding, non-polyadenylated RNAs, known as EBERs are the most abundantly expressed viral transcripts in latently EBV infected cells. We found the specific role of EBERs in cell cycle progression, resistance against chemotherapeutic drug and cellular invasion in gastric cancer cells in vitro. Ectopic expression of EBERs upregulates the expression of IL-6 and activate its downstream STAT3, which is significantly involved in downregulating the expression of cell cycle inhibitor genes p21 and p27. Stable expression of EBERs regulates the activation of pFAK and pPAK1 and the expression of anti-metastatic genes RhoGDI and KAI-1 in gastric cancer cells. In addition, administration of neu-IL-6 antibody and dominant negative STAT3β reduces chemoresistance and inhibits invasion of EBERs-expressing gastric cancer cells. Our results thus revealed a novel role of EBERs in the coordination of IL-6-STAT3 signaling pathway to chemoresistance and cellular migration.