Nicotine up-regulates SLC7A5 expression depending on TRIM29 in non-small cell lung cancer.
Nicotine up-regulates SLC7A5 expression depending on TRIM29 in non-small cell lung cancer.
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DOI：
10.1016/j.gendis.2023.04.016
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发表时间：
2024-03
期刊：
影响因子：
6.8
通讯作者：
Xia, Pu
中科院分区：
文献类型：
--
作者：
Liu, Dahua;Ren, Haolin;Wen, Guimin;Xia, Pu
非小细胞肺癌(NSCLC)是一种严重威胁人类健康的恶性肿瘤。腺癌(LUAD)和鳞癌(LUSC)是NSCLC的两种常见类型。它们分别起源于支气管上皮的腺状细胞和鳞状细胞。识别肿瘤发生过程中的基因变化有助于为患者选择合适的治疗方法。CD98是一种异源二聚体跨膜糖蛋白，由重链和轻链组成。CD98重链(CD98 Heavy Chain，CD98hc)，又称4F2hc或SLC3A2，是一种85 kDa的II型跨膜糖蛋白，由胞内区(NH2末端)、单链跨膜区和巨大的胞外区(COOH末端)组成。CD98hc可与CD98轻链LAT1(SLC7A5)通过二硫键结合形成CD98蛋白。1 SLC7A5是一个由501个氨基酸残基组成的12倍跨膜螺旋束蛋白。1 CD98的过表达与非小细胞肺癌的发生发展密切相关。因此，我们筛选了SLC3A2和SLC7A5在吸烟和不吸烟的LUSC和LUAD患者中的表达谱。此外，我们还试图确定尼古丁诱导LUSC和LUAD细胞SLC7A5表达的机制。利用癌症基因组图谱(TCGA)数据库分析不同吸烟习惯的LUAD和LUSC患者SLC3A2和SLC7A5的mRNA水平。与匹配的正常组织相比，LUAD和LUSC组织中SLC3A2和SLC7A5的mRNA水平较高(图3)。S1a、B)。在吸烟和不吸烟的LUSC或LUAD患者中，SLC3A2的表达没有差异(图4)。S1C)。LUAD患者中吸烟患者SLC7A5的表达高于不吸烟患者(图3)。S1D)。在TCGA数据库中筛选NSCLC队列中的差异表达基因后，共鉴定出SLC3A2高、低组差异表达基因660个，其中上调446个，下调214个；SLC7A5高、低组间差异表达基因409个，下调210个。热图和火山曲线被用来可视化每组中的不同基因(图。S2、3A、B)。基于上调和下调的基因进行京都基因和基因组百科全书(KEGG)途径分析。上调的基因主要集中在代谢方面，而下调的基因主要与免疫功能有关(图3)。S2、3C)。基因本体论(GO)分析表明，上调的基因主要富含染色体分离、核分裂和染色体分离，而下调的基因主要富含免疫应答、组织动态平衡和INF-γ应答(图2)。S2、3D)。这些数据证实了SLC3A2和SLC7A5作为一个整体发挥作用。相关分析显示，LUAD吸烟组表皮生长因子受体(EGFR)与TRIM29、NFKB1呈正相关，与SLC3A2、SLC7A5、SERPINB5呈负相关，而非吸烟组与SLC3A2、SLC7A5呈正相关。在吸烟和不吸烟的LUAD患者中，EGFR和TRIM29之间的相关性被逆转(图1A)。这表明尼古丁可能是通过TRIM29改变LUAD患者SLC7A5表达的一个因素。在吸烟和不吸烟的LUSC患者中，这些基因与各自的…呈正相关
Non-small cell lung cancer (NSCLC) is a malignant tumor that poses a serious threat to human health. Adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are two common types of NSCLC. They originate from glandular and squamous cells of the bronchial epithelium, respectively. Identifying gene changes during tumorigenesis is conducive to the selection of suitable treatment methods for patients. CD98 is a heterodimeric transmembrane glycoprotein, which is composed of a heavy chain and a light chain. 1 CD98 heavy chain (CD98hc), also known as 4F2hc or SLC3A2, is an 85 kDa type II transmembrane glycoprotein, which consists of a cytoplasmic region (NH2 terminal), a single chain transmembrane region, and a huge extracellular region (COOH terminal). 1 CD98hc can combine with the CD98 light chain, LAT1 (SLC7A5), to form CD98 protein through disulfide bonds. 1 SLC7A5 is a 12 times transmembrane helix bundle protein composed of 501–535 amino acid residues. 1 The overexpression of CD98 is closely related to the occurrence and development of NSCLC. Therefore, we screened the expression profiles of SLC3A2 and SLC7A5 in smoking and non-smoking patients with LUSC and LUAD. In addition, we attempted to determine the mechanisms underlying nicotine-induced SLC7A5 expression in LUSC and LUAD cells.The mRNA levels of SLC3A2 and SLC7A5 in patients with LUAD and LUSC with different smoking habits were analyzed using The Cancer Genome Atlas (TCGA) database. Compared with matched normal tissues, SLC3A2 and SLC7A5 mRNA levels were higher in LUAD and LUSC tissues (Fig. S1A, B). No difference in SLC3A2 expression was observed between smoking and non-smoking LUSC or LUAD patients (Fig. S1C). SLC7A5 expression was higher in smoking patients with LUAD than in non-smoking patients (Fig. S1D). After screening the differentially expressed genes in the NSCLC cohort in the TCGA database, 660 genes with differential expression were identified between SLC3A2 high and low groups, including 446 up-regulated genes and 214 down-regulated genes, while 409 up-regulated genes and 210 down-regulated genes were identified between SLC7A5 high and low groups. Heatmaps and volcano curves were used to visualize the different genes in each group (Fig. S2, 3A, B). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed based on up-regulated and down-regulated genes. Up-regulated genes were mainly enriched in metabolism, whereas down-regulated genes were related to immune function (Fig. S2, 3C). Gene Ontology (GO) enrichment analysis demonstrated that the up-regulated genes were mainly enriched for chromosome segregation, nuclear division, and chromosome separation, whereas the down-regulated genes were mainly enriched in immune responses, tissue homeostasis, and INF-γ responses (Fig. S2, 3D). These data confirmed that SLC3A2 and SLC7A5 function together as a whole. Correlation analysis showed that epidermal growth factor receptor (EGFR) was positively correlated with TRIM29 and NFKB1, and negatively correlated with SLC3A2, SLC7A5, and SERPINB5 in smoking patients with LUAD, while it was positively correlated with SLC3A2 and SLC7A5 in non-smoking patients (Fig. 1 A). The correlation between EGFR and TRIM29 was reversed in smoking and non-smoking patients with LUAD (Fig. 1 A). This indicates that nicotine may be a factor that changes SLC7A5 expression through TRIM29 in LUAD patients. In both smoking and non-smoking LUSC patients, these genes were positively correlated with each …
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DOI：
10.1016/j.biocel.2016.11.005
发表时间：
2016-12-01
影响因子：
4
作者：
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通讯作者：
Sethi, Tariq
影响因子：
4
作者：
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影响因子：
2.9
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
10.6
作者：
Zheng L;Feng Z;Tao S;Gao J;Lin Y;Wei X;Zheng B;Huang B;Zheng Z;Zhang X;Liu J;Shan Z;Chen Y;Chen J;Zhao F
通讯作者：
Zhao F