Jiacheng Zhong1, Xiaohu Ren1, Zhihong Chen1, Hang Zhang1, Li Zhou1, Jianhui Yuan1, Ping Li1, Xiao Chen1, Wei Liu1, Desheng Wu1, Xifei Yang1, Jianjun Liu2. 1. Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, No 8 Longyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China. 2. Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, No 8 Longyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China. Electronic address: junii8@126.com.
Abstract
OBJECTIVE: Although SET(I2PP2A) and miRNAs are reported to play a pivotal role in lung cancer, the underlying mechanisms have remained obscure. To address this issue, we investigated how miRNAs and SET participate in the progression of lung cancer. METHODS: miRNAs that target SET were predicted from multiple miRNA databases. Three human NSCLC cell lines and two normal lung cell lines were used to evaluate aberrant miRNA and SET expressions. A dual luciferase reporter assay system was employed to verify the interaction between miRNA and SET. Stable miRNA knockdown and SET overexpression in A549 cells were achieved through lentivirus transfection; the corresponding influences on lung cancer progression were also examined. RESULTS: In this study, A549 was the sole cell line to lack SET/TAF-Iα expression, which was inversely correlated with the up-regulation of miR-21-5p. SET was subsequently revealed as the direct target site of miR-21-5p in A549 cells. The stable miR-21-5p knockdown and SET/TAF-Iα overexpression were shown to markedly enhance the expression of SET/TAF-Iα and to inhibit the migration, invasion, proliferation as well as the in vivo tumorigenicity of A549 cells. CONCLUSION: We suggest that SET/TAF-Iα might be a tumor suppressing factor regulated by miR-21-5p in lung adenocarcinoma. This might provide a target for lung adenocarcinoma therapy.
OBJECTIVE: Although SET(I2PP2A) and miRNAs are reported to play a pivotal role in lung cancer, the underlying mechanisms have remained obscure. To address this issue, we investigated how miRNAs and SET participate in the progression of lung cancer. METHODS: miRNAs that target SET were predicted from multiple miRNA databases. Three humanNSCLC cell lines and two normal lung cell lines were used to evaluate aberrant miRNA and SET expressions. A dual luciferase reporter assay system was employed to verify the interaction between miRNA and SET. Stable miRNA knockdown and SET overexpression in A549 cells were achieved through lentivirus transfection; the corresponding influences on lung cancer progression were also examined. RESULTS: In this study, A549 was the sole cell line to lack SET/TAF-Iα expression, which was inversely correlated with the up-regulation of miR-21-5p. SET was subsequently revealed as the direct target site of miR-21-5p in A549 cells. The stable miR-21-5p knockdown and SET/TAF-Iα overexpression were shown to markedly enhance the expression of SET/TAF-Iα and to inhibit the migration, invasion, proliferation as well as the in vivo tumorigenicity of A549 cells. CONCLUSION: We suggest that SET/TAF-Iα might be a tumor suppressing factor regulated by miR-21-5p in lung adenocarcinoma. This might provide a target for lung adenocarcinoma therapy.
Authors: Valentina V Nenasheva; Irina V Makarova; Ekaterina A Stepanenko; Stanislav A Antonov; Ekaterina V Novosadova; Anastasia R Narsullaeva; Larisa V Kozikova; Ekaterina A Polteva; Lyudmila A Sleptsova; Natalya A Shcherbatova; Nella V Khaidarova; Lyudmila E Andreeva; Vyacheslav Z Tarantul Journal: In Vitro Cell Dev Biol Anim Date: 2021-05-21 Impact factor: 2.416