Yang Shu Lin, Guan Huan Qin, Yang Hong Bao, Chen Yao, Huang Xiao Ying, Chen Lei, Shen Zhi Fa, Wang Liang Xing
Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medicine Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Department of pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2022 Sep 2;12:940234. doi: 10.3389/fonc.2022.940234. eCollection 2022.
This study aimed to explore the expression and effect of the nuclear receptor subfamily 2 group F member 6 (NR2F6) gene in non-small cell lung cancer (NSCLC) and provide an experimental basis for the targeted therapy of NSCLC.
First, the expression of NR2F6 in lung cancer tissues was analyzed using the Gene Expression Omnibus and the Cancer Genome Atlas (TCGA) databases, and the expression of NR2F6 in lung cancer tissues and cells was verified by Western blotting and quantitative polymerase chain reaction. Next, the relationship between NR2F6 expression and the clinicopathological features of lung cancer was analyzed immunohistochemistry, and the relationship between NR2F6 expression and prognosis was analyzed using the Kaplan-Meier Plotter. The influence of NR2F6 knockdown on the proliferation capacity of lung cancer cells was then verified at cell level. Finally, the expression of heterogeneous nuclear ribonucleoprotein D (HNRNPD) in lung cancer tissue was analyzed using the TCGA database and immunohistochemistry. The impact of HNRNPD knockdown on the proliferation capacity of lung cancer cells was verified at cell level, and the relationship between NR2F6 and HNRNPD was verified by co-immunoprecipitation.
NR2F6 was highly expressed in lung cancer tissues and cells, and its expression was positively correlated with the depth of invasion, lymphatic metastasis, and clinical stage of lung cancer. High expression of NR2F6 in lung cancer was also significantly associated with poor prognosis. At cell level, NR2F6 knockdown was found to inhibit the proliferation of H460 and H358 in lung cancer cells. Furthermore, the TCGA database and immunohistochemical results showed that HNRNPD was highly expressed in lung cancer tissues and was highly consistent with NR2F6 expression in these tissues. Knockdown of HNRNPD also inhibited the proliferation of lung cancer cells. The co-immunoprecipitation experiment verified that NR2F6 interacted with HNRNPD.
NR2F6 may interact with HNRNPD to jointly regulate the progression of lung cancer, and this conclusion provides a new experimental basis for the study of the molecular targeted therapy of NSCLC.
本研究旨在探讨核受体亚家族2组F成员6（NR2F6）基因在非小细胞肺癌（NSCLC）中的表达及作用，为NSCLC的靶向治疗提供实验依据。
首先，利用基因表达综合数据库（Gene Expression Omnibus）和癌症基因组图谱（TCGA）数据库分析NR2F6在肺癌组织中的表达情况，并通过蛋白质免疫印迹法和定量聚合酶链反应验证NR2F6在肺癌组织和细胞中的表达。接下来，采用免疫组织化学方法分析NR2F6表达与肺癌临床病理特征的关系，利用Kaplan-Meier Plotter分析NR2F6表达与预后的关系。然后在细胞水平验证NR2F6基因敲低对肺癌细胞增殖能力的影响。最后，利用TCGA数据库和免疫组织化学分析肺癌组织中异质性核糖核蛋白D（HNRNPD）的表达情况。在细胞水平验证HNRNPD基因敲低对肺癌细胞增殖能力的影响，并通过免疫共沉淀验证NR2F6与HNRNPD的关系。
NR2F6在肺癌组织和细胞中高表达，其表达与肺癌的浸润深度、淋巴结转移及临床分期呈正相关。肺癌中NR2F6的高表达也与不良预后显著相关。在细胞水平，发现NR2F6基因敲低可抑制肺癌细胞中H460和H358的增殖。此外，TCGA数据库和免疫组织化学结果显示，HNRNPD在肺癌组织中高表达，且与这些组织中NR2F6的表达高度一致。HNRNPD基因敲低也抑制了肺癌细胞的增殖。免疫共沉淀实验证实NR2F6与HNRNPD相互作用。
NR2F6可能与HNRNPD相互作用共同调节肺癌的进展，这一结论为NSCLC分子靶向治疗的研究提供了新的实验依据。
