Breast cancer is a malignant tumor with high morbidity and lethality. Its pathogenesis is related to the abnormal expression of many genes. The peroxisome proliferator-activated receptors (PPARs) are a class of ligand-dependent transcription factors in the nuclear receptor superfamily. They can regulate the transcription of a large number of target genes, which are involved in life activities such as cell proliferation, differentiation, metabolism, and apoptosis, and regulate physiological processes such as glucose metabolism, lipid metabolism, inflammation, and wound healing. Further, the changes in its expression are associated with various diseases, including breast cancer. The experimental reports related to “PPAR” and “breast cancer” were retrieved from PubMed since the discovery of PPARs and summarized in this paper. This review (1) analyzed the roles and potential molecular mechanisms of non-coordinated and ligand-activated subtypes of PPARs in breast cancer progression; (2) discussed the correlations between PPARs and estrogen receptors (ERs) as the nuclear receptor superfamily; and (3) investigated the interaction between PPARs and key regulators in several signaling pathways. As a result, this paper identifies PPARs as targets for breast cancer prevention and treatment in order to provide more evidence for the synthesis of new drugs targeting PPARs or the search for new drug combination treatments.

Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.

Breast cancer is the most commonly diagnosed cancer, and its global impact is increasing. Its onset and progression are influenced by multiple cues, one of which is the disruption of the internal circadian clock. Cryptochrome 2 (Cry2) genetic dysregulation may lead to the development of some diseases and even tumors. In addition, post-translational modifications can alter the Cry2 function. Here, we aimed to elucidate the post-translational regulations of Cry2 and its role in breast cancer pathogenesis. We identified p300-drived acetylation as a novel Cry2 post-translational modification, which histone deacetylase 6 (HDAC6) could reverse. Furthermore, we found that Cry2 inhibits breast cancer proliferation, but its acetylation impairs this effect. Finally, bioinformatics analysis revealed that genes repressed by Cry2 in breast cancer were mainly enriched in the NF-κB pathway, and acetylation reversed this repression. Collectively, these results indicate a novel Cry2 regulation mechanism and provide a rationale for its role in breast tumorigenesis.

Background: Endometrial cancer (EC) is one of the malignant tumors in the female reproductive system, and effective screening is urgently needed to reduce mortality. At present, the main screening method for endometrial cancer is ultrasound combined with curettage and pathological examination. We plan to explore a non-invasive, convenient, and low-cost new screening method for EC, providing a more convenient way for early screening of EC. Methods: We included a total of 11 patients with stage IA EC, and collected 8-10ml of blood, pathological paraffin sections, and vaginal lavage fluid for each patient. The collection of vaginal lavage fluid was performed before the patient’s curettage or hysteroscopy for pathological examination. And perform high-throughput sequencing and further analysis on it. Results: In 11 cases with matched tumor and blood tissues, the extracted ctDNA concentration was significantly higher in vaginal lavage fluid than in plasma. The average and median MAF of different samples from paired tissue patients were significantly higher in vaginal lavage supernatant and sediment than in plasma. The types of genomic changes in the supernatant of vaginal lavage fluid are relatively consistent with those in the sediment and tumor tissue samples, but significantly different from those in the plasma. In addition, among the six most frequently mutated genes in this study, the consistency between vaginal lavage fluid supernatant and vaginal lavage fluid precipitation and tumor tissue genomic changes was significantly higher than in plasma. According to the results of 11 cases that provided tumor tissue samples, the genomic changes detected between the supernatant or precipitate of vaginal lavage fluid and tumor tissue were significantly consistent compared to those detected between tumor tissue and plasma. The potential targets for targeted treatment of endometrial cancer (KRAS, PIK3CA, MLH1, MSH6, POLE, PTEN) showed more significant changes in the supernatant of vaginal lavage fluid. Conclusion: The supernatant/precipitate of vaginal lavage fluid has significant clinical significance for early screening of endometrial cancer and may also have potential clinical value in guiding targeted therapy and evaluating prognosis. Vaginal lavage fluid gene sequencing may serve as a new method for initial screening of endometrial cancer.