Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) mediating chemotherapeutic drug effects and metastasis in pancreatic cancer (PC) are key reasons for the poor prognosis of this disease. lncRNA growth arrest-specific 5 (GAS5) is reported to be a tumor suppressor in multiple cancers. However, the functions of GAS5 and its related miRNAs in PC are poorly understood. This study explored the potential functions and mechanisms of GAS5 in PC gemcitabine resistance and metastasis. The results show that overexpression of GAS5 suppressed the proliferation, migration, gemcitabine resistance, stem cell-like properties, and epithelial-mesenchymal transition (EMT) of PC cells by directly binding to and suppressing miR-221 expression and enhancing suppressor of cytokine signaling 3 (SOCS3) expression. The effects of miR-221 overexpression on proliferation, migration, gemcitabine resistance, stem cell-like properties, and EMT inhibition were reversed by SOCS3 overexpression in PC cells. Additionally, GAS5 promoted gemcitabine-induced tumor growth and metastasis inhibition, as determined by Ki-67 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), bioluminescence imaging, and the detection of cell-like properties and EMT in vivo. Thus, lncRNA GAS5 functioned as a competing endogenous RNA for miR-221, and it suppressed cell growth, metastasis, and gemcitabine resistance in PC by regulating the miR-221/SOCS3 pathway mediating EMT and tumor stem cell self-renewal.
基金：
National Natural Science Foundation of China[81702942, 81702872]
第一作者机构：[1]Shanghai Jiao Tong Univ, Dept Intervent Radiol, Tongren Hosp, Sch Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Dept Intervent Radiol, Tongren Hosp, Sch Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China[*1]Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, China.
推荐引用方式(GB/T 7714)：
Liu Bingyan,Wu Shaoqiu,Ma Jun,et al.lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer[J].MOLECULAR THERAPY-NUCLEIC ACIDS.2018,13:472-482.doi:10.1016/j.omtn.2018.09.026.
APA：
Liu, Bingyan,Wu, Shaoqiu,Ma, Jun,Yan, Shuo,Xiao, Zhengguang...&Mao, Aiwu.(2018).lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer.MOLECULAR THERAPY-NUCLEIC ACIDS,13,
MLA：
Liu, Bingyan,et al."lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer".MOLECULAR THERAPY-NUCLEIC ACIDS 13.(2018):472-482
医学