MiR-137 promotes anoikis through modulating the AKT signaling pathways in Pancreatic Cancer.
MiR-137 promotes anoikis through modulating the AKT signaling pathways in Pancreatic Cancer.
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MiR-137 通过调节胰腺癌中的 AKT 信号通路促进失巢凋亡
DOI：
10.7150/jca.44037
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发表时间：
2020
影响因子：
3.9
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Li L;He Z;Zhu C;Chen S;Yang Z;Xu J;Bi N;Yu C;Sun C
失巢抵抗是肿瘤进展过程中转移性癌细胞存活的一个基本特征。然而，胰腺癌(PC)失巢耐药的机制仍不清楚。MicroRNA-137(miR-137)是一种肿瘤抑制因子，通过靶向多个癌基因来抑制癌细胞的增殖和侵袭。然而，miR-137对PC细胞失巢凋亡的影响及其分子机制尚不清楚。在这里，我们证明了miR-137在诱导失巢模型后以时间依赖的方式下调。功能分析表明miR-137在体内外均能促进胰腺癌细胞的失巢凋亡。根据临床数据库的生物信息分析，我们预测巴西林(PXN)是miR-137的靶点。此外，TCGA分析表明，PXN与PC的发展密切相关。通过功能丧失研究，我们证明PXN是miR-137在PC细胞失巢凋亡中的功能靶点。此外，我们还发现PXN促进了AKT信号通路的激活，AKT信号通路参与了癌细胞的失巢凋亡。综上所述，我们的发现表明miR-137在失巢失巢过程中发挥着新的作用，可能成为检测和治疗PC的潜在靶点。
Anoikis resistance is a fundamental feature of the survival of metastatic cancer cells during cancer progression. However, the mechanisms underlying anoikis resistance in pancreatic cancer (PC) are still unclear. MicroRNA-137 (miR-137) is a tumor suppressor that inhibits the proliferation and invasion of cancer cells through targeting multiple oncogenes. However, the effects and molecular mechanism of miR-137 on anoikis of PC are still unclear. Here we demonstrated that miR-137 was downregulated after the induction of anoikis model in time dependent. Function assays revealed that miR-137 promoted the pancreatic cancer cells anoikis in vitro and vivo. According to bioinformation analysis of clinical databases, we predicted that paxillin (PXN) was a target of miR-137. Further, TCGA analysis revealed that PXN was closely associated with the development of PC. Through loss-of-function studies, we demonstrated that PXN was a functional target of miR-137 on anoikis of PC cells. Moreover, we found that PXN promoted the activation of the AKT signaling pathways which was involving in the cancer cells anoikis. Together, our findings reveal that miR-137 plays a novel role during anoikis and may serve as a potential target for the detection and treatment of PC.