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固醇调节元件结合转录因子 1 促进头颈部鳞状细胞癌的增殖和迁移。

Sterol regulatory element binding transcription factor 1 promotes proliferation and migration in head and neck squamous cell carcinoma.

机构信息

Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

出版信息

PeerJ. 2023 Apr 17;11:e15203. doi: 10.7717/peerj.15203. eCollection 2023.

Abstract

BACKGROUND

Sterol-regulatory element-binding protein 1 (SREBP1) is a transcription factor involved in lipid metabolism that is encoded by sterol regulatory element binding transcription factor 1(SREBF1). SREBP1 overexpression is associated with the progression of several human tumors; however, the role of SREBP1 in head and neck squamous cell carcinoma (HNSC) remains unclear.

METHODS

SREBF1 expression in pan-cancer was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data, and the association between SREBF1 expression and clinical characteristics of HNSC patients was examined using the UALCAN database. Enrichment analysis of SREBF1-related genes was performed using the Cluster Profiler R package. TCGA database was used to investigate the relationship between immune cell infiltration and SREBF1 expression. CCK-8, flow cytometry, and wound healing assays were performed to investigate the effect of SREBF1 knockdown on the proliferation and migration of HNSC cells.

RESULTS

SREBF1 was significantly upregulated in several tumor tissues, including HNSC, and SREBF1 overexpression was positively correlated with sample type, cancer stage, tumor grade, and lymph node stage in HNSC patients. Gene enrichment analysis revealed that SREBF1 is associated with DNA replication and homologous recombination. SREBF1 upregulation was positively correlated with the infiltration of cytotoxic cells, B cells, T cells, T helper cells, and NK CD56 bright cells in HNSC. Knockdown of SREBF1 inhibited the proliferation and migration of HNSC cells (Hep2 and TU212) and induced apoptosis by downregulating the expression of steroidogenic acute regulatory protein-related lipid transfer 4 (STARD4).

CONCLUSIONS

SREBF1 may promote HNSC proliferation, migration and inhibit apoptosis by upregulating STARD4 and affecting the level of immune cell infiltration.

摘要

背景

固醇调节元件结合蛋白 1(SREBP1)是一种参与脂质代谢的转录因子,由固醇调节元件结合转录因子 1(SREBF1)编码。SREBP1 过表达与几种人类肿瘤的进展有关;然而,SREBP1 在头颈部鳞状细胞癌(HNSC)中的作用尚不清楚。

方法

使用癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据分析 SREBF1 在泛癌中的表达,并使用UALCAN 数据库检查 SREBF1 表达与 HNSC 患者临床特征之间的关系。使用 Cluster Profiler R 包对 SREBF1 相关基因进行富集分析。TCGA 数据库用于研究免疫细胞浸润与 SREBF1 表达的关系。CCK-8、流式细胞术和划痕愈合实验用于研究 SREBF1 敲低对 HNSC 细胞增殖和迁移的影响。

结果

SREBF1 在几种肿瘤组织中显著上调,包括 HNSC,并且 SREBF1 过表达与 HNSC 患者的样本类型、癌症分期、肿瘤分级和淋巴结分期呈正相关。基因富集分析表明 SREBF1 与 DNA 复制和同源重组有关。SREBF1 的上调与 HNSC 中细胞毒性细胞、B 细胞、T 细胞、T 辅助细胞和 NK CD56 明亮细胞的浸润呈正相关。SREBF1 敲低抑制了 HNSC 细胞(Hep2 和 TU212)的增殖和迁移,并通过下调类固醇急性调节蛋白相关脂质转移蛋白 4(STARD4)的表达诱导细胞凋亡。

结论

SREBF1 可能通过上调 STARD4 并影响免疫细胞浸润水平来促进 HNSC 的增殖、迁移和抑制凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9555/10117388/9aeab3132f93/peerj-11-15203-g001.jpg

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