Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Int J Mol Sci. 2020 May 1;21(9):3213. doi: 10.3390/ijms21093213.
microRNA-143(miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression of miR-143 is associated with a favorable tumor immune microenvironment of estrogen receptor (ER)-positive breast cancer patients which result in improved survival. Two major publicly available breast cancer cohorts; The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. The miR-143 high expression group was associated with increased infiltration of anti-cancer immune cells and decreased pro-cancer immune cells, as well as enrichment of the genes relating to T helper (Th1) cells resulting in improved overall survival (OS) in ER-positive breast cancer patients. To the best of our knowledge, this is the first study to demonstrate that high expression of miR-143 in cancer cells associates with a favorable tumor immune microenvironment, upregulation of anti-cancer immune cells, and suppression of the pro-cancer immune cells, associating with better survival of the breast cancer patients.
miR-143(miR-143)是一种众所周知的肿瘤抑制性 microRNA,通过靶向各种恶性肿瘤中的 KRAS 信号通路发挥抗肿瘤作用。我们假设 miR-143 通过靶向 KRAS 及其效应分子来抑制乳腺癌的进展。我们进一步假设 miR-143 的高表达与雌激素受体(ER)阳性乳腺癌患者有利的肿瘤免疫微环境相关,从而提高生存率。使用了两个主要的公开可用的乳腺癌队列;癌症基因组图谱(TCGA)和乳腺癌国际联合会分子分类学(METABRIC)。miR-143 高表达组与抗癌免疫细胞的浸润增加和促癌免疫细胞的浸润减少相关,以及与 Th1 细胞相关基因的富集相关,从而导致 ER 阳性乳腺癌患者的总生存率(OS)提高。据我们所知,这是第一项表明癌细胞中 miR-143 的高表达与有利的肿瘤免疫微环境、抗癌免疫细胞的上调以及促癌免疫细胞的抑制相关,从而与乳腺癌患者的更好生存相关的研究。