Retracted Article: Long noncoding RNA ANRIL knockdown increases sensitivity of non-small cell lung cancer to cisplatin by regulating the miR-656-3p/SOX4 axis

Abstract

Long noncoding RNAs (lncRNAs) are implicated in the development of chemoresistance in many cancers. However, the effect and mechanism of lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) on cisplatin (CDDP) resistance in non-small cell lung cancer (NSCLC) remain unclear. The levels of ANRIL, microRNA (miR)-656-3p and sex-determining region Y-related high-mobility group box 4 (SOX4) in NSCLC tissues and cells were detected by quantitative real-time polymerase chain reaction or western blotting. Cell viability, apoptosis, migration and epithelial-to-mesenchymal transition (EMT) were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT assay), flow cytometry, trans-well assays and western blotting, respectively. The xenograft model was established using CDDP-resistant NSCLC cells. The target association between miR-656-3p and ANRIL or SOX4 was validated by luciferase reporter assay and RNA immunoprecipitation. ANRIL expression was increased in CDDP-resistant NSCLC tissues and cells. Knockdown of ANRIL decreased cell viability, migration and EMT but induced apoptosis in CDDP-resistant NSCLC cells. Moreover, silencing of ANRIL reduced xenograft tumor growth in vivo. miR-656-3p was targeted by ANRIL and its exhaustion attenuated the suppressive role of ANRIL knockdown in CDDP resistance in NSCLC cells. SOX4 acted as a target of miR-656-3p and was positively regulated by ANRIL. Collectively, interference of ANRIL repressed CDDP resistance through promoting apoptosis and inhibiting cell viability, migration and EMT by up-regulating miR-656-3p and down-regulating SOX4, indicating a new target to improve the chemotherapeutic efficacy in NSCLC.