在缺氧条件下，低氧诱导因子1α（HIF1α）和低氧诱导因子2α（HIF2α）通过Sox2和Oct4的表达来调控非小细胞肺癌的去分化。

HIF1α and HIF2α regulate non-small-cell lung cancer dedifferentiation via expression of Sox2 and Oct4 under hypoxic conditions.

作者信息

Xiong Shuanglong, Wang Donglin, Tang Yin, Lu Songmei, Huang Lumi, Wu Zhijuan, Lei Shuangyi, Liang Guanzhong, Yang Dan, Li Dairong, Li Yan

机构信息

Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, People's Republic of China.

出版信息

Gene. 2023 May 5;863:147288. doi: 10.1016/j.gene.2023.147288. Epub 2023 Feb 16.

DOI:10.1016/j.gene.2023.147288

PMID:36804853

Abstract

OBJECTIVE

To explore HIF1α and HIF2α regulate the dedifferentiation of lung cancer cells under hypoxic conditions through Sox2 and Oct4.

MATERIALS AND METHODS

HIF1α, HIF2α, Sox2 and Oct4 expression was analysed in lung cancer tissues. We analysed sphere formation by single-cell of differentiated lung cancer under hypoxia, and detected the expression of CD133, CD44, Sox2, Oct4, HIF1α and HIF2α. We knocked out HIF1α, HIF2α, Sox2 or Oct4 in cells, cultured the cells under hypoxic conditions and detected CD133 and CD44 using western blotting. We also detected the apoptosis rate of cells with HIF1α, HIF2α, Sox2 or Oct4 knockout.

RESULTS

There was more sphere formation of differentiated lung cancer cells under hypoxic conditions than of control cells under normoxic conditions. These newly formed spheres highly expressed CD133 and CD44. TCGA database showed high expression of HIF1α and HIF2α in lung cancer tissues. After knocking out HIF1α and HIF2α, the expression of Sox2, Oct4, CD133 and CD44 decreased significantly, and after knocking out Sox2 or Oct4, the expression of CD133 and CD44 decreased.

CONCLUSION

HIF1α and HIF2α regulate non-small-cell lung cancer dedifferentiation through Sox2 and Oct4 under hypoxic conditions.

摘要

目的

探讨缺氧条件下低氧诱导因子1α（HIF1α）和低氧诱导因子2α（HIF2α）通过性别决定区Y框蛋白2（Sox2）和八聚体结合转录因子4（Oct4）调控肺癌细胞去分化的机制。

材料与方法

分析肺癌组织中HIF1α、HIF2α、Sox2和Oct4的表达情况。对分化型肺癌细胞进行单细胞缺氧成球实验，并检测细胞表面抗原CD133、CD44、Sox2、Oct4、HIF1α和HIF2α的表达。通过基因敲除技术分别敲除细胞中的HIF1α、HIF2α、Sox2或Oct4，在缺氧条件下培养细胞，采用蛋白质免疫印迹法检测CD133和CD44的表达。同时检测敲除HIF1α、HIF2α、Sox2或Oct4后细胞的凋亡率。

结果

缺氧条件下分化型肺癌细胞的成球能力明显高于常氧条件下的对照细胞。新形成的细胞球高表达CD133和CD44。肿瘤基因组图谱（TCGA）数据库显示肺癌组织中HIF1α和HIF2α高表达。敲除HIF1α和HIF2α后，Sox2、Oct4、CD133和CD44的表达显著降低；敲除Sox2或Oct4后，CD133和CD44的表达也降低。