Details

Autor(en) / Beteiligte

• Ramji, Kavita
• Kulesza, Dorota Weronika
• Chouaib, Salem
• Kaminska, Bozena

Titel

Off-target effects of plasmid-transcribed shRNAs on NF[kappa]B signaling pathway and cell survival of human melanoma cells

Ist Teil von

• Molecular biology reports, 2013-12, Vol.40 (12), p.6977

Ort / Verlag

Dordrecht: Springer Nature B.V

Erscheinungsjahr

2013

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF[kappa]B) are transcription factors involved in cell survival, inflammation and metastasis. Constitutively activated STAT3 is found in many cancers, including melanoma. To study the crosstalk between STAT3 and NF[kappa]B signaling and its role in regulation of cancer cell survival, we used RNA interference (RNAi) to down-regulate STAT3 expression in human melanoma cells. RNAi strategies including double-stranded RNA, small interfering RNA (siRNA), short hairpin RNA (shRNA) and microRNA are widely used to knock down disease-causing genes in a targeted fashion. We found that shRNAs up-regulate non-specific NF[kappa]B activity, while siRNA directed against STAT3 specifically increase NF[kappa]B activity. The basal survival of melanoma cells is unaffected by STAT3 knockdown--likely due to activation of pro-survival NF[kappa]B signaling. Whereas, owing to off-target effects, plasmid-transcribed shRNA affects melanoma survival. Our data show that shRNA-mediated gene silencing induces non-specific or off-target effects that may influence cell functions.[PUBLICATION ABSTRACT]