Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway

Abstract

This study aim to explore the effect of down-regulation of PRR11 (proline-rich protein 11) on the proliferation, invasion, migration, Wnt/β-catenin signaling pathway and EMT of osteosarcoma cells. Methods: Immunohistochemical staining, fluorescent quantitative PCR and western blotting were used to detect the expression level of PRR11 in osteosarcoma tissues and osteosarcoma cells. After SiRNA down-regulated the expression level of PRR11, CCK8 was used to detect cell proliferation ability, Transwell chamber to detect cell invasion ability, scratch test to detect cell migration ability, and flow cytometry to detect cell apoptosis. Western blotting was used to detect the expression levels of wnt/β-catenin pathway related proteins and key epithelial-mesenchymal transition proteins. Results: PRR11 is highly expressed in osteosarcoma tissues, and its expression level is related to tumor size, Enneking stage of tumor, lymph node metastasis and patient prognosis. The low expression of PRR11 can inhibit the proliferation, migration and invasion of osteosarcoma cells, and promote apoptosis. Down-regulating the expression of PRR11 will inhibit the expression of Wnt pathway related proteins β-catenin and p-GSK-3β, enhance the expression of p-β-catenin, GSK-3β, and increase the expression of downstream genes CyclinD1 and c-Myc in the Wnt pathway. At the same time, the expression of PRR11 was down-regulated, the epithelial marker E-cadherin was significantly increased, and the expression levels of mesenchymal markers Vimentin and Fibronectin were significantly reduced. Conclusion: Down-regulation of PRR11 can inhibit the proliferation, migration and invasion of osteosarcoma cells, and its mechanism may be related to down-regulation of PRR11 to inhibit the Wnt/β-catenin signaling pathway and thus prevent the EMT process. Therefore, PRR11 may be used as an oncogene to promote the occurrence and development of osteosarcoma, and is a potential prognostic indicator and therapeutic target in osteosarcoma.

The roles of glycolysis in osteosarcoma

“…As an important intracellular transcription factor, c-myc promotes glycolysis by transactivating and promoting the expression of genes related to glycolysis ( Gruning et al, 2010 ; Han et al, 2012 ). Furthermore, as the target of several oncogenes or tumor suppressor genes, c-myc participates in regulating many signal pathways, such as MEK-ERK, Wnt/β-catenin, PI3K/AKT/mTOR, and STAT3/c-myc ( Han et al, 2012 ; Li K. et al, 2021 ; Tang et al, 2022 ). In 2012, Han et al (2012) found that c-myc overexpression in OS significantly enhanced the invasive ability of OS cells by promoting the MEK-ERK pathway.…”

PRR11 in Malignancies: Biological Activities and Targeted Therapies

“…Mechanically, PRR11 knockdown decreased β-catenin and p-GSK-3β and increased p-β-catenin and GSK-3β, thus inactivating Wnt/β-catenin signaling. In addition, PRR11 knockdown also increased the expression of E-cadherin, but reduced vimentin and fibronectin in the EMT signaling [ 21 ]. Above all, PRR11 might be an independent and reliable biomarker and therapeutic target for osteosarcoma patients.…”

“…Subsequently, in vitro and in vivo models were utilized for evaluation of PRR11 in tumorigenesis. In vitro, cellular proliferation and cell-cycle progression were evidently boosted by PRR11 in TSCC, ESCC, NSCLC, BRCA, GC, CRC, HCC, HCCA, Pancreatic cancer, Ovarian cancer and Osteosarcoma [ 4 , 5 , 7 , 8 , 10 , 12 , 13 , 14 , 16 , 19 , 21 ]. Similarly, in in vivo models, PRR11 promoted xenograft tumor growth in tumor size, weight and Ki-67 expression in TSCC, NSCLC, GC, CRC, HCC and Ovarian cancer [ 2 , 6 , 8 , 9 , 11 , 13 , 19 , 20 ].…”

“…Compared with non-tumorous tissues, PRR11 is evidently upregulated in tumor tissues, including ESCC, NSCLC, CRC, HCC, Pancreatic cancer, Ovarian cancer and Osteosarcoma, which would contribute to the improvement of clinical diagnosis in these cancers [ 2 , 4 , 7 , 9 , 14 , 15 , 19 , 20 , 21 , 34 ]. More importantly, PRR11 also serves as a prognostic biomarker for several human cancers.…”

“…More importantly, PRR11 also serves as a prognostic biomarker for several human cancers. Considering the clinical features and prognosis of these patients, PRR11 is positively correlated with earlier tumor invasion, advanced clinical stage, TNM classification, more lymph node metastasis and higher Ki-67 ratio, which usually are accompanied by shorter overall survival in TSCC, NSCLC, BRCA, GC, HCC, Pancreatic cancer, Ovarian cancer and Osteosarcoma [ 1 , 5 , 7 , 11 , 12 , 13 , 14 , 20 , 21 , 22 , 40 , 54 ]. Therefore, PRR11 acts as a promising prognostic indicator in a limited number of human cancers, gradually manifesting its potential application for targeted therapies ( Table 1 and Table 2 ).…”