Fu Chuang, Jiang Wen, Wang Chong, Song Sheng-Jie, Tao Hao, Zhang Xin-Guo, Li Wen-Ting, Jin Xin, Yu Bin-Bing, Hao Jia-Jie, Sun Wen-Juan, Bai Jie, Shi Zhi-Zhou
Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China.
Department of Thoracic Surgery, the Affiliated Hospital of Kunming University of Science and Technology and First People's Hospital of Yunnan Province, Kunming, People's Republic of China.
Anim Cells Syst (Seoul). 2024 Nov 1;28(1):536-550. doi: 10.1080/19768354.2024.2417458. eCollection 2024.
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.
食管鳞状细胞癌（ESCC）是一种侵袭性恶性肿瘤，到目前为止，长链非编码RNA（lncRNA）AP001885.4在包括ESCC在内的癌症中的作用尚不清楚。应用GEPIA数据库来鉴定食管癌（ESCA）中差异表达和与预后相关的基因。采用CCK-8、集落形成、蛋白质免疫印迹和qRT-PCR方法研究AP001885.4在食管癌变中的作用及机制。通过分析GEPIA数据库中的TCGA数据，筛选出两个lncRNAs。AP001885.4过表达且与ESCC患者的不良预后呈正相关，而LINC001786表达下调且与预后不良呈负相关。敲低AP001885.4可抑制ESCC细胞的增殖和集落形成。重要的是，沉默AP001885.4可下调c-myc的表达。机制上，敲低AP001885.4可降低METTL3的表达以及c-myc mRNA的m6A修饰，且METTL3正向调控c-myc。此外，敲低AP001885.4可减少组蛋白乳酸化和NF-κB（p65）的表达，并且蛋白质乳酸化抑制剂（2-DG，2-脱氧-D-葡萄糖和草氨酸盐）和NF-κB抑制剂（JSH-23）也可降低c-myc的表达。因此，我们的研究结果表明，AP001885.4通过组蛋白乳酸化和NF-κB（p65）依赖性转录激活以及METTL3介导的c-myc mRNA稳定性促进食管鳞状细胞癌细胞的增殖。
