Zhu Yusha, Chen Qiao Yi, Jordan Ashley, Sun Hong, Roy Nirmal, Costa Max
Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY 10100, USA.
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shanxi 710000, P.R. China.
Oncol Rep. 2021 Aug;46(2). doi: 10.3892/or.2021.8105. Epub 2021 Jun 10.
Nickel (Ni) compounds are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) and are known to be carcinogenic to the lungs. In our previous study, special AT‑rich sequence‑binding protein 2 (SATB2) was required for Ni‑induced BEAS‑2B cell transformation. In the present study, a pathway that regulates the expression of SATB2 protein was investigated in Ni‑transformed BEAS‑2B cells using western blotting and RT‑qPCR for expression, and soft agar, migration and invasion assays for cell transformation. Runt‑related transcription factor 2 (RUNX2), a master regulator of osteogenesis and an oncogene, was identified as an upstream regulator for SATB2. Ni induced RUNX2 expression and initiated BEAS‑2B transformation and metastatic potential. Previously, miRNA‑31 was identified as a negative regulator of SATB2 during arsenic‑induced cell transformation, and in the present study it was identified as a downstream target of RUNX2 during carcinogenesis. miR‑31 expression was reduced in Ni‑transformed BEAS‑2B cells, which was required to maintain cancer hallmarks. The expression level of miR‑31 was suppressed by RUNX2 in BEAS‑2B cells, and this increased the expression level of SATB2, initiating cell transformation. Ni caused the repression of miR‑31 by placing repressive marks at its promoter, which in turn increased the expression level of SATB2, leading to cell transformation.
镍（Ni）化合物被国际癌症研究机构（IARC）列为1类致癌物，已知对肺部具有致癌性。在我们之前的研究中，镍诱导的BEAS-2B细胞转化需要富含AT序列结合蛋白2（SATB2）。在本研究中，我们使用蛋白质印迹法和RT-qPCR检测镍转化的BEAS-2B细胞中SATB2蛋白的表达调控途径，并通过软琼脂、迁移和侵袭试验检测细胞转化情况。成骨主调节因子及癌基因 runt相关转录因子2（RUNX2）被确定为SATB2的上游调节因子。镍诱导RUNX2表达并引发BEAS-2B细胞转化及转移潜能。此前，miRNA-31在砷诱导的细胞转化过程中被确定为SATB2的负调节因子，在本研究中，它在致癌过程中被确定为RUNX2的下游靶点。在镍转化的BEAS-2B细胞中，miR-31表达降低，这是维持癌症特征所必需的。在BEAS-2B细胞中，RUNX2抑制miR-31的表达水平，从而增加SATB2的表达水平，引发细胞转化。镍通过在miR-31启动子上放置抑制性标记来抑制其表达，进而增加SATB2的表达水平，导致细胞转化。
