Breast cancer has become the most common malignant tumor worldwide with 70% of breast cancer being hormone receptor-positive (Waks and Winer, 2019). While the prognosis of hormone receptor-positive breast cancer is better than that of HER2-positive or triple-negative breast cancer, some patients may not be sensitive to endocrine therapy. This may reduce the efficacy in treating existing tumors and also increase the chance of relapse or metastasis (Loibl et al., 2021). The PI3K/AKT/mTOR signaling pathway and CDK4/6-E2F1 signaling pathway play crucial roles in the relapse and metastasis of advanced hormone receptor-positive breast cancer (Vasan et al., 2019, Spring et al., 2020). Several drugs that target these pathways have been applied in clinical practice. PP1A is the α subunit of protein phosphatase 1, research has revealed that PP1A promotes colorectal cancer growth and metastasis via the activation of the ERK/MAPK signaling pathway (Sun et al., 2019). Evidence also suggests that PP1A may promote melanoma progression via the Hippo-YAP1 signaling pathway (Ma et al., 2021). However, the function of PP1A in hormone receptor-positive breast cancer remains unclear.

The function of the transcription factor E2F1 in hormone receptor-positive breast cancer is well described, aberrant activation of CDK4/6 promotes E2F1-dependent oncogene expression (Fang et al., 2020). Some long non-coding RNAs (lncRNAs) recruit special transcription factors for binding to the promoters of target genes, recent studies have revealed that target gene enhancers may encode lncRNAs called enhancer RNAs, which bind with transcription factors and adjust nearby gene expression (Zhang et al., 2019). A potential enhancer sequence exists approximately 480,000 base pairs (bp) away from PP1A. This enhancer region encodes long intergenic non-protein coding RNA 2754 (LINC02754). However, it is currently unknown whether LINC02754 can function as an enhancer RNA to recruit transcription factors and adjust the expression of the nearby PP1A gene.

Yes-associated protein 1 (YAP1) is the core protein of the Hippo signaling pathway, specifically, the kinase MST1/2 phosphorylates LATS1/2, which then phosphorylates YAP1. The phosphorylated YAP1 is then degraded in the cytoplasm through the ubiquitin-proteasome system. The non-phosphorylated YAP1 moves to nucleus and interacts with the transcription factor TEAD4, which promotes expression of downstream oncogenes, such as CTGF and Cyr61 (Dey et al., 2020).The protein-protein interaction network STRING database indicates that PP1A may interact with YAP1 (Szklarczyk et al., 2021). However, whether PP1A interacts with YAP1 and influences tumor progression via YAP1 signaling in hormone receptor-positive breast cancer remains unclear.