NRIP1 is activated by C-JUN/C-FOS and activates the expression of PGR, ESR1 and CCND1 in luminal A breast cancer

Abstract

Using chip array assays, we identified differentially expressed genes via a comparison between luminal A breast cancer subtype and normal mammary ductal cells from healthy donors. In silico analysis confirmed by western blot and immunohistochemistry revealed that C-JUN and C-FOS transcription factors are activated in luminal A patients as potential upstream regulators of these differentially expressed genes. Using a chip-on-chip assay, we identified potential C-JUN and C-FOS targets. Among these genes, the NRIP1 gene was revealed to be targeted by C-JUN and C-FOS. This was confirmed after identification and validation with transfection assays specific binding of C-JUN and C-FOS at consensus binding sites. NRIP1 is not only upregulated in luminal A patients and cell lines but also regulates breast cancer-related genes, including PR, ESR1 and CCND1. These results were confirmed by NRIP1 siRNA knockdown and chip array assays, thus highlighting the putative role of NRIP1 in PGR, ESR1 and CCND1 transcriptional regulation and suggesting that NRIP1 could play an important role in breast cancer ductal cell initiation.

Circular RNA-related CeRNA network and prognostic signature for patients with oral squamous cell carcinoma

“…Hsa_circ_0004771, hsa_circ_0005991, and hsa_circ_0060927 are spliced by nuclear receptor interacting protein 1 (NRIP1), amyloid beta precursor protein binding family B member 2 (APBB2), and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), respectively, which play essential roles in tumor proliferation, migration, and apoptosis. NRIP1, a coregulator of several nuclear receptors and transcription factors, can act as a co-activator or Frontiers in Pharmacology frontiersin.org corepressor and is upregulated in a variety of tumor types, including gastric cancer (Liang and Li, 2020), gastric adenocarcinoma (Fang and Lu., 2020), esophageal squamous cell carcinoma (Ni et al, 2018), and breast cancer (Binato et al, 2021). APBB2 is an articulated protein characterized for its function in amyloid precursor protein processing (Tanahashi Frontiers in Pharmacology frontiersin.org and Tabira, 2002).…”

Integrating network pharmacology and pharmacological evaluation to investigate the anticancer effects of Duranta erecta Linn. Verbenaceae in breast cancer

“…The other targets determined as core targets in this study were also supported by previous studies as oncogenic driven proteins. That is the case of EZH2 53,54 , IL6 55,56 , JUN 57 , and MMP9 58,59 .…”

Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS

“…A previous study revealed that c-FOS protooncogene expression was induced by estrogen in MCF7 breast cancer cells (34). Recently, Binato et al (35) reported that c-FOS and c-JUN proteins are induced in luminal A-type breast cancer cells, and that nuclear receptor-interacting protein 1 (NRIP1) was consequently augmented by the complex. Furthermore, it was found that expression levels of the progesterone receptor, estrogen receptor 1 and cyclin D1 were upregulated by NRIP1, suggesting a link between c-FOS and the proliferation of breast cancer cells (35).…”

“…Recently, Binato et al (35) reported that c-FOS and c-JUN proteins are induced in luminal A-type breast cancer cells, and that nuclear receptor-interacting protein 1 (NRIP1) was consequently augmented by the complex. Furthermore, it was found that expression levels of the progesterone receptor, estrogen receptor 1 and cyclin D1 were upregulated by NRIP1, suggesting a link between c-FOS and the proliferation of breast cancer cells (35). In addition, c-FOS is transcriptionally induced by ETS Transcription Factor ELK1 in bladder cancer (36).…”