Abstract：
A cancer-inhibiting role of mesenchyme homeobox 2 (MEOX2) has been observed in several malignancies. However, the association between MEOX2 and breast carcinoma has not been addressed. This research focused on investigating the possible relevance of MEOX2 in breast carcinoma. Initial expression analysis by TCGA data uncovered low levels of MEOX2 in breast carcinoma. We then confirmed that MEOX2 was poorly expressed in clinical tumor specimens of breast carcinoma by real-time quantitative PCR and immunoblotting assays. Moreover, low levels of MEOX2 in breast carcinoma patients were found to be correlated with reduced overall survival. A series of cellular function assays showed that the forced expression of MEOX2 had anticancer effects, including the inhibition of cell proliferation, the induction of G0-G1 phase arrest, the restraint of metastatic potential, and the enhancement of chemosensitivity. Further analysis revealed that MEOX2 negatively modulated the phosphatidyl-inositol-3 kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) and extracellular signal-regulated kinase (ERK1/2) pathways. Reactivation of AKT by a chemical activator reversed MEOX2-mediated anticancer effects. An in vivo xenograft assay validated the anticancer function of MEOX2 in breast carcinoma. Taken together, these data show that MEOX2 exerts a cancer-inhibiting role in breast carcinoma by affecting the PI3K/AKT/mTOR and ERK1/2 pathways. This work suggests MEOX2 as a new contributor for breast carcinoma progression, which may be a candidate target for anticancer therapy development.
摘要：
已在几种恶性肿瘤中观察到间充质同源盒2（MEOX2）的癌症抑制作用。然而,MEOX2与乳腺癌之间的关联尚未得到解决.这项研究的重点是探讨MEOX2在乳腺癌中的可能相关性。通过TCGA数据的初始表达分析揭示了乳腺癌中MEOX2的低水平。然后，我们通过实时定量PCR和免疫印迹法证实了MEOX2在乳腺癌的临床肿瘤标本中表达不良。此外，研究发现,乳腺癌患者MEOX2水平低与总生存率降低相关.一系列的细胞功能检测表明，MEOX2的强制表达具有抗癌作用，包括抑制细胞增殖，诱导G0-G1期停滞，抑制转移潜能，和增强化学敏感性。进一步分析显示MEOX2负调节磷脂酰肌醇-3激酶(PI3K)/AKT/哺乳动物雷帕霉素靶标(mTOR)和细胞外信号调节激酶(ERK1/2)途径。化学激活剂对AKT的再激活可逆转MEOX2介导的抗癌作用。体内异种移植试验验证了MEOX2在乳腺癌中的抗癌功能。一起来看,这些数据表明,MEOX2通过影响PI3K/AKT/mTOR和ERK1/2通路在乳腺癌中发挥抑癌作用.这项工作表明MEOX2是乳腺癌进展的新贡献者，这可能是抗癌治疗发展的候选靶标。
