Bermúdez Gisella, Bernal Camila, Otalora Andrea, Sanchez Paula, Nardocci Gino, Cañas Alejandra, Lopez-Kleine Liliana, Montecino Martín, Rojas Adriana
Institute of Human Genetics, Facultad de Medicina, Pontificia Universidad Javeriana Bogotá, Bogotá 110231, Colombia.
Facultad de Medicina, Universidad Nacional de Colombia, Bogotá 110211, Colombia.
Curr Issues Mol Biol. 2023 Aug 24;45(9):7075-7086. doi: 10.3390/cimb45090447.
Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal-epithelial transition processes. In this paper, we identified (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings.
We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF. In addition, we performed shRNA-mediated knockdown of RUNX2 in this lung adenocarcinoma cell line to confirm the regulatory role of RUNX2 in expression.
We observed RUNX2 overexpression in cell lines and primary cultured lung cancer cells. Interestingly, we found that lncRNA TALAM1 was a target of RUNX2 and that RUNX2 exerted a negative regulatory effect on transcription.
肺癌是全球癌症死亡的主要原因。据报道，遗传和表观遗传因素在肺癌的发生和发展中起着关键作用。先前的报道表明，胚胎发育中的关键转录因子促成了这种病理过程。 runt相关转录因子（RUNX）蛋白属于胚胎发育程序的主要调节因子家族。具体而言，RUNX2是成骨细胞分化的主要转录因子（TF），它可通过调节细胞凋亡和间充质-上皮转化过程参与前列腺癌、甲状腺癌和肺癌等病理状况。在本文中，我们将转移相关肺腺癌转录本1（Metastasis Associated Lung Adenocarcinoma Transcript 1）鉴定为肺癌中RUNX2 TF的遗传靶点，然后对主要发现进行了功能验证。
我们对一名被诊断为肺腺癌患者的肿瘤样本进行了染色质免疫沉淀测序（ChIP-seq）分析，以评估RUNX2 TF的靶基因。此外，我们在该肺腺癌细胞系中进行了shRNA介导的RUNX2敲低，以证实RUNX2在转移相关肺腺癌转录本1（TALAM1）表达中的调节作用。
我们在细胞系和原代培养的肺癌细胞中观察到RUNX2过表达。有趣的是，我们发现lncRNA TALAM1是RUNX2的一个靶点，并且RUNX2对其转录发挥负调节作用。
