RNA binding protein HuR promotes osteosarcoma cell progression via suppressing the miR-142-3p/HMGA1 axis.
RNA binding protein HuR promotes osteosarcoma cell progression via suppressing the miR-142-3p/HMGA1 axis.
复制标题
DOI：
10.3892/ol.2018.8855
复制
发表时间：
2018-08
期刊：
影响因子：
2.9
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Pan W;Pang J;Ji B;Wang Z;Liu C;Cheng Y;Zhang L
本研究旨在探讨人抗原R（HuR）在骨肉瘤（OS）细胞生长过程中的作用及其机制。结果表明，与正常癌旁组织相比，骨肉瘤组织中HuR的mRNA和蛋白水平均显著上调。HuR表达与miR-142- 3 p表达呈负相关，但与高迁移率族AT-Hook 1（HMGA 1）呈正相关。此外，HuR的敲低抑制OS细胞的活力，上皮间质转化和促进细胞凋亡。HuR被确定为在HMGA 1上具有结合位点，直接结合HMGA 1，增加HMGA 1 mRNA的稳定性和表达。miR-142- 3 p过表达可减弱HuR对HMGA 1表达的促进作用，且miR-142- 3 p可直接与HMGA 1 3′非翻译区（UTR）结合。此外，具有突变的miR-142- 3 p结合位点的HMGA 1 3′UTR对HuR改变没有反应。最后，通过HMGA 1过表达减弱甚至逆转HuR敲低的抑制;因此，本研究的结果表明，RNA结合蛋白HuR可能通过与miR-142- 3 p竞争性结合HMGA 1而促进OS细胞进展。
The present study aimed to study the roles and underlying mechanisms of human antigen R (HuR) in osteosarcoma (OS) cell progression. It was determined that the HuR mRNA and protein levels were significantly upregulated in OS tissues, compared with that in normal adjacent tissues. HuR expression was negatively associated with miR-142-3p expression, but positively with High Mobility Group AT-Hook 1 (HMGA1). Additionally, knockdown of HuR inhibited OS cells viability, epithelial-mesenchymal transition and promoted cell apoptosis. HuR was determined to harbor binding sites on HMGA1, directly binding to HMGA1, increasing HMGA1 mRNA stability and expression. Notably, the promotion of HuR on HMGA1 expression was attenuated via miR-142-3p overexpression, and miR-142-3p could directly bind to HMGA1 3′untranslated region (UTR). Furthermore, HMGA1 3′UTR with a mutated miR-142-3p binding site did not respond to HuR alterations. Finally, the inhibition of HuR knockdown was attenuated or even reversed via HMGA1 overexpression; therefore, the results of the present study indicated that RNA binding protein HuR may facilitate OS cell progression via competitively binding to HMGA1 with miR-142-3p.
登录
查看更多内容
RNA结合蛋白DND1通过在miR-221结合位点稳定BIM mRNA来促进乳腺癌的凋亡。
影响因子：
--
作者：
Cheng F;Pan Y;Lu YM;Zhu L;Chen S
通讯作者：
Chen S
影响因子：
7.7
作者：
Dai, Ning;Ji, Fei;Avruch, Joseph
通讯作者：
Avruch, Joseph
影响因子：
12.4
作者：
Conte A;Paladino S;Bianco G;Fasano D;Gerlini R;Tornincasa M;Renna M;Fusco A;Tramontano D;Pierantoni GM
通讯作者：
Pierantoni GM
影响因子：
3.7
作者：
Picci P
通讯作者：
Picci P
DOI：
10.1158/1541-7786.mcr-15-0448
发表时间：
2016-07
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Romeo C;Weber MC;Zarei M;DeCicco D;Chand SN;Lobo AD;Winter JM;Sawicki JA;Sachs JN;Meisner-Kober N;Yeo CJ;Vadigepalli R;Tykocinski ML;Brody JR
通讯作者：
Brody JR