title: Epstein-Barr virus-encoded small non-coding RNAs induce cancer cell chemoresistance and migration.
abstract: 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.
authors.affiliation: Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Aditi Sengupta
authors.initials: AS
authors.lastname: Banerjee
authors.forename: Anindita Deb
authors.initials: AD
authors.lastname: Pal
authors.forename: Subrata
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004351:Drug Resistance / Q000187:drug effects*; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000821:virology
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D058727:RNA, Small Untranslated; D012367:RNA, Viral; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Chemoresistance; EBERs; Epstein–Barr virus; Gastric cancer; IL-6; Migration; STAT3