Upregulation of PAIP1 promotes the gallbladder tumorigenesis through regulating PLK1 level

Abstract

Background: Increasing evidence suggests that elevated expression of polyA-binding protein-interacting protein 1 (PAIP1) is associated with cancer development and progression. However, how PAIP1 promotes gallbladder cancer (GBC) is still unclear.Methods: Two GBC tissue-derived cell lines, NOZ and GBC-SD cells, were used in this study. Assays of cell proliferation, colony formation, apoptosis, and xenograft tumor model were performed to examine the tumorigenic effects of PAIP1. Immunohistochemical (IHC) staining was used to examine the expression level of PAIP1 in both patient GBC tissues and mouse tumors. Microarray and bioinformatics analysis were used to explore the targets of PAIP1. Quantitative polymerase chain reaction (qPCR) and western blot analysis were used to validate PAIP1-mediated targets.Results: We found that upregulated PAIP1 expression was correlated with GBC. Knockdown of PAIP1 in gallbladder cells alleviated cell proliferation, promoted apoptosis, and inhibited xenograft tumor growth.Gene microarray analysis showed that stable silencing of PAIP1 altered various gene expressions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that PAIP1 regulates cell cycle progression. Finally, we found that the PLK1 kinase, a key regulator of cell cycle, was regulated by PAIP1 at the transcriptional and protein levels. PLK1 level was positively correlated with PAIP1 level in both mouse tumors and GBC tissues. PAIP1 interacted with PLK1, and rescue of PAIP1 could recover PLK1 protein level and inhibit apoptosis.Conclusions: Our data suggest that PAIP1 contributes to GBC progression likely through regulating PLK1 level. Since upregulated PAIP1 expression is positively associated with GBC, PAIP1 may act as a clinical prognostic biomarker of GBC.

PAIP1 regulates expression of immune and inflammatory response associated genes at transcript level in liver cancer cell

“…Previous studies reported that PAIP1 knockdown inhibit the cell viability in a variety of cancer cell lines ( Bi et al, 2021 ; Guan et al, 2019 ; Li et al, 2019 ; Piao et al, 2018 ; Wang et al, 2019b ; Wang et al, 2019c ; Xie et al, 2020 ). Our study showed that PAIP1 knockdown can inhibit cell viability of liver cancer, which is consistent with previous studies.…”

“…PAIP1 is a RNA binding protein, by which PAIP1 participates in regulation of translation ( Craig et al, 1998 ; Ivanov et al, 2019 ; Martineau et al, 2008 ; Martineau et al, 2014 ) and mRNA decay ( Grosset et al, 2000 ). PAIP1 are highly expressed in many types of cancer ( Bi et al, 2021 ; Guan et al, 2019 ; Li et al, 2019 ; Piao et al, 2018 ; Wang et al, 2019b ; Wang et al, 2019c ; Xie et al, 2020 ), inducing liver cancer ( Kim et al, 2020 ). However, the genome-widely regulated targets and mechanism of PAIP1 in liver cancer is still unclear.…”

“…Moreover, PAIP1 protein interacts with ubiquitin ligases UBR5 and WWP2 to achieve ubiquitin degradation ( Lv, Zhang & Gao, 2014 ; Muñoz Escobar et al, 2015 ). As for the biology function, PAIP1 are highly expressed in many types of cancer, inducing breast cancer ( Piao et al, 2018 ), lung adenocarcinoma ( Wang et al, 2019c ), pancreatic cancer ( Guan et al, 2019 ), cervical cancer ( Li et al, 2019 ), and gastric cancer ( Wang et al, 2019b ), human tongue squamous cell carcinoma ( Xie et al, 2020 ) and gallbladder cancer ( Bi et al, 2021 ). Knocking down PAIP1 in a variety of cancer cell lines can inhibit the proliferation and metastasis of cancer cells, and/or induce apoptosis and cell cycle arrest ( Bi et al, 2021 ; Guan et al, 2019 ; Li et al, 2019 ; Piao et al, 2018 ; Wang et al, 2019b ; Wang et al, 2019c ; Xie et al, 2020 ).…”

“…As for the biology function, PAIP1 are highly expressed in many types of cancer, inducing breast cancer ( Piao et al, 2018 ), lung adenocarcinoma ( Wang et al, 2019c ), pancreatic cancer ( Guan et al, 2019 ), cervical cancer ( Li et al, 2019 ), and gastric cancer ( Wang et al, 2019b ), human tongue squamous cell carcinoma ( Xie et al, 2020 ) and gallbladder cancer ( Bi et al, 2021 ). Knocking down PAIP1 in a variety of cancer cell lines can inhibit the proliferation and metastasis of cancer cells, and/or induce apoptosis and cell cycle arrest ( Bi et al, 2021 ; Guan et al, 2019 ; Li et al, 2019 ; Piao et al, 2018 ; Wang et al, 2019b ; Wang et al, 2019c ; Xie et al, 2020 ). Mechanistically, PAIP1 inhibits lung cancer cell proliferation and epithelial-mesenchymal transition related metastasis by regulating AKT/GSK-3 β signaling pathway ( Wang et al, 2019c ).…”

“…PAIP1 knockdown could decrease the expression of Ki67 and Pcna, and increased Bax/Bcl2 index and caspase-3 expression in human tongue squamous cell carcinoma ( Xie et al, 2020 ). PAIP1 promotes gallbladder cancer through regulating expression of PLK1 ( Bi et al, 2021 ). Results of these studies indicated that PAIP1 is a potential prognostic biomarker for cancer.…”