Prognoses and genomic analyses of proteasome 26S subunit, ATPase (PSMC) family genes in clinical breast cancer.

Tzu-Jen Kao,Yen-Hsi Liu,Chih-Yang Wang,Hoang Dang Khoa Ta,Chung-Che Wu,Yung-Fu Wu,Gangga Anuraga,Kuen-Haur Lee,Jian-Ying Chuang,Nam Nhut Phan

doi:10.18632/aging.203345

Abstract

Breast cancer is a complex disease, and several processes are involved in its development. Therefore, potential therapeutic targets need to be discovered for these patients. Proteasome 26S subunit, ATPase gene (PSMC) family members are well reported to be involved in protein degradation. However, their roles in breast cancer are still unknown and need to be comprehensively researched. Leveraging publicly available databases, such as cBioPortal and Oncomine, for high-throughput transcriptomic profiling to provide evidence-based targets for breast cancer is a rapid and robust approach. By integrating the aforementioned databases with the Kaplan–Meier plotter database, we investigated potential roles of six PSMC family members in breast cancer at the messenger RNA level and their correlations with patient survival. The present findings showed significantly higher expression profiles of PSMC2, PSMC3, PSMC4, PSMC5, and PSMC6 in breast cancer compared to normal breast tissues. Besides, positive correlations were also revealed between PSMC family genes and ubiquinone metabolism, cell cycle, and cytoskeletal remodeling. Meanwhile, we discovered that high levels of PSMC1, PSMC3, PSMC4, PSMC5, and PSMC6 transcripts were positively correlated with poor survival, which likely shows their importance in breast cancer development. Collectively, PSMC family members have the potential to be novel and essential prognostic biomarkers for breast cancer development.

Highlights

In 2020, breast cancer accounted for 30% of all types of cancer in women in the United States
Salvage therapy for breast cancer patients includes fulvestrant [1, 2], cyclin-dependent kinase 4/6 inhibitors [3], aromatase inhibitors combined with everolimus (a mammalian analog of rapamycin which acts as a mammalian target of rapamycin inhibitor) [4], and histone deacetylase (HDAC) inhibitors [5]
According to our results from an Oncomine analysis of mRNA expressions of PSMC2, PSMC3, PSMC4, PSMC5, and PSMC6, these members are highly upregulated in breast cancer tissues; we chose breast cancer to perform further bioinformatics analyses (Figure 1)

Summary

Introduction

In 2020, breast cancer accounted for 30% of all types of cancer in women in the United States. High expression of B-cell lymphoma 2 was detected in nearly 70% of metastatic breast cancer patients, and treatment with a selective inhibitor improved apoptosis in a preclinical model of breast cancer [6, 7]. The PSMC family is comprised of six members, namely PSMC1, PSMC2, PSMC3, PSMC4, PSMC5, and PSMC6, which partially constitute formation of the 19S regulatory complex. This complex plays an important role in regulating the 26S proteasome, which in turn, catalyzes the unfolding and translocation of substrates into the 20S proteasome. Previous studies showed that PSMC6 promotes osteoblast apoptosis and cancer cell proliferation, while PSMC2 inhibits apoptosis. Knockdown of PSMC3IP resulted in suppression of xenograft proliferation and tumorigenesis [17]

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Conclusion