High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer.

Rui Yang,Sihui Yu,Mingjun Ma,Jiawen Zhang,Xi Li,Sufang Wu

doi:10.3389/fonc.2021.742017

Abstract

Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is frequently lost in breast cancer samples and is considered as a tumor suppressor. The roles and mechanisms of PAMR1 in other types of cancers are still unclear. In our present study, we identified PAMR1 as an invasion-related regulator in cervical cancer. Public database and immunohistochemical (IHC) analysis showed that the expression level of PAMR1 in cervical cancer tissues was lower than that in normal cervix tissues and was negatively related to clinicopathologic features. The high expression of PAMR1 also predicted a better prognosis of cervical cancer patients. CCK8, Transwell, and wound-healing assays demonstrated that knockdown of PAMR1 facilitated the proliferation, migration, and invasion of cervical cancer cells. Additionally, gene set enrichment analysis (GSEA) showed a variety of cancer-related pathways potentially activated or suppressed by PAMR1. Moreover, we verified that PAMR1 inhibited MYC target and mTORC1 signaling pathways. In conclusion, our study revealed the suppressor role of PAMR1 in cervical cancer, providing a new insight into the molecular mechanism of cervical cancer progression.

Highlights

Cervical cancer is the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 [1]
We found that PAMR1 was one of most downregulated differentially expressed genes (DEGs) in invasive cervical cancer (p = 3.13e-6, logFC = −3.635, Figure 1A)
We found that PAMR1 was negatively correlated to individual cancer stage (Figure 1F), but not tumor grade of cervical cancer (Supplemental Figure S1B)

Summary

Introduction

Cervical cancer is the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 [1]. Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is located at chromosome 11p13 and originally considered to be a regeneration-associated muscle protease (RAMP) [5]. It is predominantly expressed in normal skeletal muscle and brain tissues, downregulated in the muscles of Duchenne muscular dystrophy (DMD), and correlated with type 2 diabetes and cardiac pathological remodeling [5,6,7,8]. PAMR1 is inactivated by promoter hypermethylation in breast cancer, so it has been considered as a tumor suppressor [10]. There is no relevant research on the role of PAMR1 in the tumorigenesis and progression of cervical cancer

Methods

Results

Discussion

Conclusion