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长链非编码 RNA ADAMTS9-AS1 通过调控 miR-5009-3p/NPNT 轴抑制肺腺癌细胞的干性。

LncRNA ADAMTS9-AS1 inhibits the stemness of lung adenocarcinoma cells by regulating miR-5009-3p/NPNT axis.

机构信息

Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, Henan, China.

Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, Henan, China.

出版信息

Genomics. 2023 May;115(3):110596. doi: 10.1016/j.ygeno.2023.110596. Epub 2023 Mar 2.

DOI:10.1016/j.ygeno.2023.110596
PMID:36870548
Abstract

We sought to extend our observation of LncRNA ADAMTS9-AS1 and to specifically uncover its role on the stemness of lung adenocarcinoma (LUAD) cancer cells. ADAMTS9-AS1 was poorly expressed in LUAD. The high ADAMTS9-AS1 expression was positively associated with overall survival. ADAMTS9-AS1 overexpression attenuated the colony-forming capacity and reduced stem cell-like population of LUAD cancer stem cells (CSCs). Furthermore, ADAMTS9-AS1 overexpression increased E-cadherin expression in addition to the downregulated expressions of Fibronectin and Vimentin in LUAD spheres. In vitro results also confirmed the ADAMTS9-AS1's inhibitory effect on the growth of LUAD cells. Moreover, the antagonistic repression of miR-5009-3p levels with the expression of ADAMTS9-AS1 and NPNT was confirmed. Finally, ADAMTS9-AS1 overexpression curbed the increasing stemness of LUDA-CSC caused by NPNT silencing, thus leading to the suppression of LUAD progression in vitro. Conclusively, ADAMTS9-AS1 negatively controls the LUAD cancer cell stemness progression through regulating miR-5009-3p/NPNT axis.

摘要

我们试图扩展对 LncRNA ADAMTS9-AS1 的观察,并特别揭示其对肺腺癌(LUAD)癌细胞干性的作用。ADAMTS9-AS1 在 LUAD 中表达水平较低。高表达的 ADAMTS9-AS1 与总生存期呈正相关。ADAMTS9-AS1 的过表达减弱了 LUAD 癌症干细胞(CSC)的集落形成能力,并降低了其干细胞样群体。此外,ADAMTS9-AS1 的过表达增加了 E-钙黏蛋白的表达,同时下调了 LUAD 球体中纤连蛋白和波形蛋白的表达。体外结果也证实了 ADAMTS9-AS1 对 LUAD 细胞生长的抑制作用。此外,还证实了 ADAMTS9-AS1 与 NPNT 共同表达对 miR-5009-3p 水平的拮抗抑制作用。最后,ADAMTS9-AS1 的过表达抑制了 NPNT 沉默引起的 LUDA-CSC 干性增加,从而抑制了 LUAD 的体外进展。综上所述,ADAMTS9-AS1 通过调节 miR-5009-3p/NPNT 轴来负调控 LUAD 癌细胞干性进展。

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