lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer.
lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer.
复制标题
lncRNA GAS5 通过靶向 miR-221/SOCS3 逆转胰腺癌中的 EMT 和肿瘤干细胞介导的吉西他滨耐药和转移
DOI：
10.1016/j.omtn.2018.09.026
复制
发表时间：
2018-12-07
期刊：
影响因子：
--
通讯作者：
Mao A
中科院分区：
文献类型：
--
作者：
Liu B;Wu S;Ma J;Yan S;Xiao Z;Wan L;Zhang F;Shang M;Mao A
在胰腺癌（PC）中，介导化疗药物作用和转移的长链非编码RNA（lncRNA）和微小RNA（miRNAs）的失调是这种疾病预后不良的关键原因。据报道，lncRNA生长抑制特异性5（GAS 5）是多种癌症中的肿瘤抑制因子。然而，GAS 5及其相关的miRNA在PC中的功能知之甚少。本研究旨在探讨GAS 5在前列腺癌吉西他滨耐药和转移中的作用及其机制。结果显示，GAS 5的过表达通过直接结合并抑制miR-221表达和增强细胞因子信号传导抑制因子3（SOCS 3）表达来抑制PC细胞的增殖、迁移、吉西他滨抗性、干细胞样性质和上皮-间质转化（EMT）。miR-221过表达对增殖、迁移、吉西他滨耐药、干细胞样特性和EMT抑制的影响被PC细胞中的SOCS 3过表达逆转。此外，GAS 5促进吉西他滨诱导的肿瘤生长和转移抑制，如通过Ki-67染色和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）、生物发光成像以及体内细胞样性质和EMT的检测所确定的。因此，lncRNA GAS 5作为miR-221的竞争性内源性RNA发挥作用，并且其通过调节介导EMT和肿瘤干细胞自我更新的miR-221/SOCS 3途径来抑制PC中的细胞生长、转移和吉西他滨耐药性。
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.
登录
查看更多内容
长链非编码RNA uc.345通过上调hnRNPL表达促进胰腺癌的肿瘤发生
影响因子：
--
作者：
Liu C;Wang J;Yuan X;Qian W;Zhang B;Shi M;Xie J;Shen B;Xu H;Hou Z;Chen H
通讯作者：
Chen H
源自骨髓间充质干细胞的外泌体的 miRNA-221 促进胃癌的致癌活性
影响因子：
4
作者：
Ma M;Chen S;Liu Z;Xie H;Deng H;Shang S;Wang X;Xia M;Zuo C
通讯作者：
Zuo C
影响因子：
--
作者：
Lu YB;Jiang Q;Yang MY;Zhou JX;Zhang Q
通讯作者：
Zhang Q
LncRNA HOTTIP 通过调节 HOXA9 调节人胰腺癌中的癌症干细胞特性
影响因子：
9.7
作者：
Fu, Zhiqiang;Chen, Changhao;Chen, Rufu
通讯作者：
Chen, Rufu
影响因子：
4.6
作者：
Kim MS;Jeong J;Seo J;Kim HS;Kim SJ;Jin W
通讯作者：
Jin W