乳腺癌
E2F1
癌症研究
小RNA
细胞生长
免疫组织化学
癌症
E2F型
肿瘤科
肺癌
生物
细胞周期
医学
内科学
基因
生物化学
遗传学
作者
Teeranut Asavasupreechar,Ryoko Saito,Yasuhiro Miki,Keiichi Tamai,Jiro Abe,Chihiro Inoue,Ikuro Sato,Viroj Boonyaratanakornkit,Hironobu Sasano
出处
期刊:Endocrine-related Cancer
[Bioscientifica]
日期:2023-05-02
卷期号:30 (7)
摘要
The presence of progesterone receptor (PR) and PR isoform B (PRB) in breast cancer is generally correlated with better clinical outcomes. Additionally, the significance of hormone-independent effects of PR/PRB correlated with better prognosis has been reported in non-small cell lung cancer (NSCLC). However, the detailed mechanism of that still remains unclear. In this study, we examined how microRNAs (miRNAs) could contribute to tumor inhibition via PR/PRB expression, in order to find miRNAs that have tumor-agnostic effects between breast cancer and NSCLC. We obtained miRNA data using human tissues of breast cancer and NSCLC from The Cancer Genome Atlas (TCGA) database and PCR array from NSCLC patients of our cohort. Subsequently, we examined the function of the miRNA through in vitro study using breast cancer cell lines. As a result, only let-7b expression was significantly correlated with PR expression in both cancers. Additionally, the expression of let-7b significantly inhibited cell proliferation by inducing PR and PRB expression in breast cancer cell lines. However, the positive correlation of let-7b and PRB required a mediated factor, E2 promoter binding factor 1 (E2F1), obtained from TCGA database analysis. In vitro experiments showed that let-7b significantly inhibited E2F1, and E2F1 significantly inhibited PRB. This study revealed that PRB inhibits the proliferation of breast cancer cells by the let-7b-E2F1 interaction. In addition, the immunohistochemical analysis in NSCLC was also consistent with these in vitro data. Our results could contribute to developing novel therapeutic strategies for patients with PR/PRB-positive cancer by targeting let-7b or PRB expression in breast cancer and possibly NSCLC.
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