title: Targeted reduction of KLF6-SV1 restores chemotherapy sensitivity in resistant lung adenocarcinoma.
abstract: Kruppel-like factor 6 splice variant 1 (KLF6-SV1) is an oncogenic splice variant of the KLF6 tumor suppressor gene that is specifically overexpressed in a number of human cancers. Previously, we have demonstrated that increased expression of KLF6-SV1 is associated with decreased survival in lung adenocarcinoma patient samples and that targeted reduction of KLF6-SV1 using siRNA induced apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Here, we demonstrate that chemoresistant lung cancer cells express increased levels of KLF6-SV1. Furthermore, targeted reduction of KLF6-SV1 using RNA interference restores chemotherapy sensitivity to lung cancer cells both in culture and in vivo through induction of apoptosis. Conversely, overexpression of KLF6-SV1 resulted in a marked reduction in chemotherapy sensitivity in a tumor xenograft model. Combined, these findings highlight a functional role for the KLF6-SV1 splice variant in the regulation of chemotherapy response in lung cancer and could provide novel insight into lung cancer therapy.
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Sangodkar
authors.forename: Analisa
authors.initials: A
authors.lastname: DiFeo
authors.forename: Lauren
authors.initials: L
authors.lastname: Feld
authors.forename: Romina
authors.initials: R
authors.lastname: Bromberg
authors.forename: Rachel
authors.initials: R
authors.lastname: Schwartz
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.forename: Esteban A
authors.initials: EA
authors.lastname: Terzo
authors.forename: Aisha
authors.initials: A
authors.lastname: Choudhri
authors.forename: Goutham
authors.initials: G
authors.lastname: Narla