Department of Cardio-thoracic Surgery, Xinhua Hospital Chongming Branch, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Environ Toxicol. 2022 Mar;37(3):504-513. doi: 10.1002/tox.23416. Epub 2021 Nov 27.
The previous study has shown that transcriptional factor MEOX1 could promote proliferation and sphere formation ability of non-small cell lung cancer (NSCLC) cells, however, we found that MEOX1 mRNA was lowly expressed in lung cancer tissues compared to that in normal adjacent tissues, and MEOX1 mRNA expression was positively correlated with the survival of lung cancer patients, especially in lung adenocarcinoma patients. Functional experiments using in vitro and in vivo experiments revealed that stable overexpression of MEOX1 significantly suppressed the proliferation ability, promoted cell cycle arrest in G2 phase, and apoptotic ability of NSCLC cells. Additionally, it was identified that MEOX1 and CCNB1 mRNA expression exhibited a negative correlation in different lung cancer tissues. Mechanistically, we indicated that MEOX1 bound to the transcriptional initiation site of CCNB1 and thus suppressed CCNB1 expression. Notably, CCNB1 overexpression rescued the inhibition of MEOX1 overexpression on NSCLC progression. This study deciphers a novel MEOX1/CCNB1 axis suppressing NSCLC progression.
先前的研究表明转录因子 MEOX1 可以促进非小细胞肺癌 (NSCLC) 细胞的增殖和球体形成能力，然而，我们发现与正常相邻组织相比，肺癌组织中 MEOX1 mRNA 的表达水平较低，并且 MEOX1 mRNA 的表达与肺癌患者的生存呈正相关，尤其是在肺腺癌患者中。使用体外和体内实验的功能实验表明，稳定过表达 MEOX1 可显著抑制 NSCLC 细胞的增殖能力，促进细胞周期停滞在 G2 期，并诱导细胞凋亡。此外，还在不同的肺癌组织中发现 MEOX1 和 CCNB1 mRNA 的表达呈负相关。在机制上，我们表明 MEOX1 与 CCNB1 的转录起始位点结合，从而抑制 CCNB1 的表达。值得注意的是，CCNB1 的过表达挽救了 MEOX1 过表达对 NSCLC 进展的抑制作用。这项研究揭示了一个新的 MEOX1/CCNB1 轴抑制 NSCLC 进展。
