Ren Shuchang, Tan Xiaohui, Fu Melinda Z, Ren Shuyang, Wu Xiaoling, Chen Tao, Latham Patricia S, Lin Paul, Man Yan-Gao, Fu Sidney W
Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.
Department of Medicine, Chengdu Military General Hospital, Chengdu, Sichuan, China.
J Cancer. 2021 Oct 20;12(23):7138-7146. doi: 10.7150/jca.63836. eCollection 2021.
Esophageal cancer (EC) is a lethal cancer with an extremely aggressive nature and poor survival rate. However, the molecular mechanisms driving the occurrence and progression of EC are not well understood. MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of protein-coding genes. miRNA-mediated gene regulation plays an important role in EC. By cross-referencing studies from NCBI, we found that microRNA-375 (miR-375) is one of the most frequently downregulated miRNAs in EC. We assessed expression of miR-375 in EC cell lines and primary EC tissues and their matched normal tissues. We found significant downregulation of miR-375 in both cell lines and EC tissues. Forced expression of miR-375 attenuated EC cell proliferation and invasion. Human epidermal growth factor receptor 2 (HER2, ERBB2), a known proto-oncogene, was identified here as one of the potential target genes of miR-375. Ectopic expression of miR-375 significantly suppressed the expression of ERBB2 and subsequently downregulated one of its target genes, vascular endothelial growth factor A (VEGFA), which is related to cancer invasion and metastasis. These findings suggest that miR-375 acts as a tumor suppressor by blocking the ERBB2/VEGFA pathway with the potential to modulate the occurrence and/ or progression of EC.
食管癌（EC）是一种具有极强侵袭性且生存率低的致命性癌症。然而，驱动EC发生和进展的分子机制尚未完全明确。微小RNA（miRNA）是调节蛋白质编码基因表达的小RNA分子。miRNA介导的基因调控在EC中发挥重要作用。通过对美国国立医学图书馆（NCBI）研究的交叉引用，我们发现微小RNA - 375（miR - 375）是EC中最常下调的miRNA之一。我们评估了miR - 375在EC细胞系、原发性EC组织及其匹配的正常组织中的表达。我们发现miR - 375在细胞系和EC组织中均显著下调。miR - 375的强制表达减弱了EC细胞的增殖和侵袭。人表皮生长因子受体2（HER2，ERBB2），一种已知的原癌基因，在此被确定为miR - 375的潜在靶基因之一。miR - 375的异位表达显著抑制了ERBB2的表达，并随后下调了其靶基因之一血管内皮生长因子A（VEGFA）的表达，VEGFA与癌症侵袭和转移相关。这些发现表明，miR - 375通过阻断ERBB2/VEGFA途径发挥肿瘤抑制作用，具有调节EC发生和/或进展的潜力。
