Replication Protein A 3 Is Associated with Hepatocellular Carcinoma Tumorigenesis and Poor Patient Survival

Abstract

Background: Replication protein A (RPA) 3 is a subunit of the RPA protein complex, which functions in multiple processes of DNA metabolism. Dysregulation of RPA1 and RPA2 has been implicated in tumor progression in several cancer types. However, the function of RPA3 in hepatocellular carcinoma (HCC) tumorigenesis has not been elucidated. Method: In this study, we investigated the function of RPA3 in HCC development by stably knocking down its expression using short hairpin RNA (shRNA) in HepG2 cell line, followed by cell proliferation, colony formation, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumor-promoting properties of RPA3. Results: Downregulation of RPA3-inhibited cell proliferation, colony formation, soft agar growth as well as invasion in HepG2 cells were observed. Stable knockdown of RPA3 significantly inhibited tumor growth in the xenograft mouse model. In addition, qRT-PCR analysis revealed that RPA3 was upregulated in human HCC tissues compared with matched noncancerous adjacent tissues (NATs). High expression of RPA3 was associated with poor overall survival and disease-free survival. Conclusion: Elevated expression of RPA3 promotes tumor progression in HCC cells. RPA3 is upregulated in HCC tissues and high expression of RPA3 is associated with poorer patient survival. Therefore, this protein may represent a novel therapeutic target for intervention of HCC and prognostic biomarker for patient survival.

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome‐Wide Association Study in Multiple Cohorts

“…[ 9 ] These findings implicate that RPA1 might play an important role in regulating the activation of EBV and host immune response against its infection, [ 18 ] while the underlying mechanisms are yet to be addressed. In addition, previous studies have demonstrated the expression of RPA1 and RPA2 are potential prognostic factors in multiple cancers, [ 17c,19 ] and likewise, RPA3 has been associated with survival of patients with gastric cancer, [ 20 ] hepatocellular cancer, [ 21 ] and NPC. [ 22 ] These findings suggest that RPA1 and other subunits of RPA complex might be important modulators for the progression of several human cancers.…”

Identification of Prognostic Model and Biomarkers for Cancer Stem Cell Characteristics in Glioblastoma by Network Analysis of Multi-Omics Data and Stemness Indices

“…RPA3, a member of the replication protein family, plays an important role in DNA repair, recombination, replication, and cell cycle regulation. RPA3 is associated with the occurrence and poor prognosis of liver cancer, as well as the aging of hematopoietic stem cells (Xiao et al, 2018;Lian X. et al, 2019;Zhang and Yu, 2020). RRM2 has been reported to be associated with the occurrence and poor survival of prostate cancer.…”

Replication Protein A (RPA) Mediates Radio-Resistance of Glioblastoma Cancer Stem-Like Cells

“…An early study aiming to identify autoantigens in breast cancer patients showed that antibodies against RPA32 can be detected prior to diagnosis [22]. In hepatocellular carcinoma and gastric cancer, higher RPA14 expression was found to correlate with a poor outcome [23,24]. Another study in bladder cancer showed that while in early stage low RPA32 levels positively correlated with patient outcome, at later stages in invasive tumors, both high RPA70 and RPA32 expression informed adverse prognosis [25].…”