Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Respiratory Medicine, The People's Hospital of Leshan, Leshan, China.
Thorac Cancer. 2018 Jan;9(1):136-141. doi: 10.1111/1759-7714.12550. Epub 2017 Nov 3.
CRTC2 is highly expressed in lung cancer and contributes to lung cancer pathogenesis; however, whether CRTC2 promotes lung cancer metastasis remains unknown. In the present study, we investigated the role of CRTC2 in lung cancer metastasis in vitro.
CRTC2 stable knockdown of lung cancer cell A549 was generated with small hairpin RNA and confirmed by quantitative reverse transcription-PCR and Western blot. Wound healing and invasion transwell assays were performed to explore migration and invasion activity, and Western blot was conducted to detect the expression of related proteins.
Suppression of CRTC2 significantly inhibited A549 cell migration and invasion in vitro. Mechanistic studies showed that knockdown of CRTC2 greatly downregulated MMP2 and MMP9 expression. CRTC2 silencing remarkably suppressed epithelial-mesenchymal transition by modulating the expression of E-cadherin and vimentin. Furthermore, suppression of CRTC2 expression significantly reduced MAPK/c-Jun N-terminal kinase activity.
CRTC2 may promote A549 migration and invasion by modulation of c-Jun N-terminal kinase-mediated epithelial-mesenchymal transition and matrix metalloproteinase expression.
CRTC2 在肺癌中高度表达,促进肺癌的发病机制;然而,CRTC2 是否促进肺癌转移尚不清楚。在本研究中,我们研究了 CRTC2 在肺癌转移中的作用。
用短发夹 RNA 构建 CRTC2 稳定敲低的肺癌细胞 A549,并通过定量逆转录-PCR 和 Western blot 进行验证。通过划痕愈合和侵袭小室实验检测迁移和侵袭活性,通过 Western blot 检测相关蛋白的表达。
抑制 CRTC2 显著抑制了 A549 细胞在体外的迁移和侵袭。机制研究表明,CRTC2 敲低显著下调 MMP2 和 MMP9 的表达。CRTC2 沉默通过调节 E-钙黏蛋白和波形蛋白的表达,显著抑制上皮-间充质转化。此外,抑制 CRTC2 表达显著降低了 MAPK/c-Jun N 末端激酶的活性。
CRTC2 可能通过调节 c-Jun N 末端激酶介导的上皮-间充质转化和基质金属蛋白酶表达促进 A549 的迁移和侵袭。