Wenjing Shi1, Liqun Ling1, Changhong Li1, Ruihao Wu1, Meijuan Zhang1, Fanggui Shao1, Yumin Wang2. 1. Department of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnosis and Translation Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, Zhejiang Province, China. 2. Department of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnosis and Translation Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, Zhejiang Province, China. wangyumin0577@wmu.edu.cn.
Abstract
PURPOSE: Our previous experiments have demonstrated that lncRNA UCA1 (UCA1) promoted cisplatin resistance in lung adenocarcinoma (LUAD). This study aimed to explore the potential downstream target genes regulated by UCA1 and how this downstream gene promotes cisplatin resistance in LUAD. METHODS: Here, we measured the expression level of Heme oxygenase1 (HO1) in LUAD cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) based on UCA1 overexpression cell lines and UCA1 knockdown cell lines. HO1 was knocked down in the UCA1 overexpression cell line, and HO1 was overexpressed in the UCA1 knockdown cell line, and the half maximal inhibitory concentration (IC50) trends were observed by adding cisplatin containing a certain concentration gradient. Cell functional assays were performed to observe the changes in the biological behavior of HO1 after overexpression and knockdown, and the tumorigenic assay in nude mice was performed to verify the effect of UCA1 in regulating the growth and cisplatin resistance of HO1 on LUAD cells in vivo. RESULTS: The results showed that HO1 and UCA1 expression were both upregulated in LUAD tissues and LUAD cisplatin-resistant cell lines, and there was a significant positive correlation between the expression of HO1 and UCA1. In vitro experiments showed that HO1 overexpression could reverse the reduced sensitivity to cisplatin caused by UCA1 knockdown in A549/DDP cells, and HO1 knockdown could reduce cisplatin resistance in A549 UCA1 overexpressing cells. Tumorigenic assays in nude mice further confirmed the role of HO1 in the regulation of UCA1 by activating the NRF2/HO1 pathway against LUAD cisplatin resistance. CONCLUSION: Our findings suggested that UCA1 regulates HO1 targets the UCA1/NRF2-HO1 pathway to exert cisplatin resistance in LUAD.
PURPOSE: Our previous experiments have demonstrated that lncRNA UCA1 (UCA1) promoted cisplatin resistance in lung adenocarcinoma (LUAD). This study aimed to explore the potential downstream target genes regulated by UCA1 and how this downstream gene promotes cisplatin resistance in LUAD. METHODS: Here, we measured the expression level of Heme oxygenase1 (HO1) in LUAD cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) based on UCA1 overexpression cell lines and UCA1 knockdown cell lines. HO1 was knocked down in the UCA1 overexpression cell line, and HO1 was overexpressed in the UCA1 knockdown cell line, and the half maximal inhibitory concentration (IC50) trends were observed by adding cisplatin containing a certain concentration gradient. Cell functional assays were performed to observe the changes in the biological behavior of HO1 after overexpression and knockdown, and the tumorigenic assay in nude mice was performed to verify the effect of UCA1 in regulating the growth and cisplatin resistance of HO1 on LUAD cells in vivo. RESULTS: The results showed that HO1 and UCA1 expression were both upregulated in LUAD tissues and LUAD cisplatin-resistant cell lines, and there was a significant positive correlation between the expression of HO1 and UCA1. In vitro experiments showed that HO1 overexpression could reverse the reduced sensitivity to cisplatin caused by UCA1 knockdown in A549/DDP cells, and HO1 knockdown could reduce cisplatin resistance in A549 UCA1 overexpressing cells. Tumorigenic assays in nude mice further confirmed the role of HO1 in the regulation of UCA1 by activating the NRF2/HO1 pathway against LUAD cisplatin resistance. CONCLUSION: Our findings suggested that UCA1 regulates HO1 targets the UCA1/NRF2-HO1 pathway to exert cisplatin resistance in LUAD.
Authors: Javier de Castro; Marina C Rodríguez; Vicenta S Martínez-Zorzano; Patricia Sánchez-Rodríguez; Jesús Sánchez-Yagüe Journal: Am J Clin Pathol Date: 2014-07 Impact factor: 2.493
Authors: Francesca Maria Consonni; Augusto Bleve; Maria Grazia Totaro; Mariangela Storto; Paolo Kunderfranco; Alberto Termanini; Fabio Pasqualini; Chiara Alì; Chiara Pandolfo; Francesco Sgambelluri; Giulia Grazia; Mario Santinami; Andrea Maurichi; Massimo Milione; Marco Erreni; Andrea Doni; Marco Fabbri; Laura Gribaldo; Eliana Rulli; Miguel Parreira Soares; Valter Torri; Roberta Mortarini; Andrea Anichini; Antonio Sica Journal: Nat Immunol Date: 2021-04-26 Impact factor: 25.606