Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 20;22(1):34.
doi: 10.1186/s12935-021-02441-6.

Periostin promotes the proliferation and metastasis of osteosarcoma by increasing cell survival and activates the PI3K/Akt pathway

Chaojian Xu #  1   2 , Ziyue Wang #  3 , Long Zhang  4 , Yi Feng  2 , Jia Lv  2 , Zhuangzhuang Wu  2 , Rong Yang  1 , Taiyong Wu  1 , Jian Li  1 , Ruhao Zhou  1 , Zhi Tian  2 , Junjun Bai  2 , Huadong Zhang  2 , Yanping Lan  2 , Zhi Lv  5   6
Affiliations

Periostin promotes the proliferation and metastasis of osteosarcoma by increasing cell survival and activates the PI3K/Akt pathway

Chaojian Xu et al. Cancer Cell Int. .

Abstract

Background: Silencing of the periostin gene (POSTN) can inhibit the biological process of several different cancers, and this inhibition may be related to down-regulation of PI3K/AKT signaling. However, the effect of POSTN on the progression, proliferation, and invasion of osteosarcoma (OS) remain unclear.

Methods: We used the Gene Expression Omnibus (GEO) database to screen datasets on in situ OS and lung metastases to identify core genes and potential pathways. We used additional bioinformatics tools to identify protein-protein interactions (PPIs) and gene networks, and selected the top seven genes whose expression had the strongest correlations with other genes.

Results: The results indicated that POSTN was a major hub gene. Subsequent analysis of gene expression profiles showed that POSTN was highly expressed in 262 cases with sarcoma and expression was closely related to poor prognosis. We also performed enrichment analysis to identify differentially expressed genes and used real-time PCR, western blotting, and immunohistochemistry analyses to measure POSTN expression in cells and tissues. Transfection of a POSTN-shRNA plasmid into cultured OS cells (Saos-2) effectively inhibited the proliferation, invasion, and migration of these cells. Taken together, our results suggest that POSTN may play a role in promoting the proliferation and metastasis of OS by activation of the PI3K/Akt signaling pathway.

Conclusions: Our results provide a preliminary characterization of the mechanism by which POSTN may regulate the migration and invasion of OS cells and also provide a theoretical basis for identifying biomarkers that have potential use for the diagnosis and treatment of OS.

Keywords: Metastasis; Osteosarcoma; POSTN (Periostin); Pathway; Proliferation.

PubMed Disclaimer

Conflict of interest statement

All of the authors agreed the publication of the paper and declare no conflicts of interests.

Figures

Fig. 1
Fig. 1
Expression of POSTN is greater in OS than normal bone cells. A qRT-PCR of POSTN in normal (C-28) and OS (MG-63, Saos-2, and I2-OS) bone cells (P < 0.0001). B Western blotting of POSTN in normal (C-28) and OS (MG-63 and Saos-2) bone cells (P = 0.007, P = 0.009). C Western blotting of POSTN in normal and OS bone tissues (P = 0.0014, n = 4). D Hematoxylin–eosin staining and immunohistochemical staining of POSTN in paraffin sections of normal and OS tumor tissues
Fig. 2
Fig. 2
Transfection of OS cells with POSTN-shRNA downregulates POSTN expression. A Fluorescence microscopy of cells in the POSTN-shRNA and Scramble-shRNA groups (transfection efficiency: 60%). B qRT-PCR of POSTN in cells transfected with POSTN-shRNA or Scramble-shRNA (P = 0.017)
Fig. 3
Fig. 3
Transfection of OS cells with POSTN-shRNA inhibits cell proliferation. A RealTime Cellular Analysis of the proliferation of cells transfected with POSTN-shRNA or Scramble-shRNA. P2: POSTN-shRNA; CON: Scramble-shRNA. B, C Western blotting of PCNA expression in cells transfected with POSTN-shRNA or Scramble-shRNA (P < 0.0001)
Fig. 4
Fig. 4
Transfection of OS cells with POSTN-shRNA inhibits cell migration and invasion. A, B Wound healing assay of OS cells transfected POSTN-shRNA or Scramble-shRNA (P = 0.0222). C, D Transwell assay of OS cells transfected POSTN-shRNA or Scramble-shRNA (P < 0.0001)
Fig. 5
Fig. 5
Transfection of OS cells with POSTN-shRNA downregulates the PI3K/AKT pathway. A, B Western blotting of AKT, p-AKT, and PI3K in cells transfected with POSTN-shRNA or Scramble-shRNA (all P < 0.0001)
Fig. 6
Fig. 6
Immunohistochemical analysis shows that MMPs have higher expression in OS tissues. A MMP-1 expression in OS and normal bone tissue. B MMP-3 expression in OS and normal bone tissue. C MMP-13 expression in OS normal bone tissue
Fig. 7
Fig. 7
Comparison of gene expression in OS lung metastasis specimens with OS non-metastasis specimens (GSE85537 and GSE37552 datasets) indicates 26 significant DEGs
Fig. 8
Fig. 8
Functional gene enrichment analysis indicates OS tissues have DEGs in multiple categories. A Cellular components. B Molecular functions. C Biological processes. D Biological pathways
Fig. 9
Fig. 9
STRING analysis of direct and indirect protein–protein interactions in OS indicates that POSTN has the most interactions. A Co-expressed gene PPI network. B DEGREE results of the top 7 genes according to the degree of connection. C Connection ranks of the 7 major genes
Fig. 10
Fig. 10
Kaplan–Meier analysis shows that OS patients with high POSTN expression have worse overall survival than those with low expression (P = 0.013)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Arndt CAS, Crist WM. Medical progress: common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 1999;341(5):342–352. doi: 10.1056/NEJM199907293410507. - DOI - PubMed
    1. Ceci F, Polverari G, Graziani T, et al. The role of F-18-FDG PET/CT in the detection of osteosarcoma recurrence. Eur J Nucl Med Mol Imaging. 2017;44(10):1712–20. doi: 10.1007/s00259-017-3698-0. - DOI - PubMed
    1. Weeden S, Grimer RJ, Cannon SR, Taminiau AHM, Uscinska BM. The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer. 2001;37(1):39–46. doi: 10.1016/S0959-8049(00)00362-2. - DOI - PubMed
    1. Takeshita S, Kikuno R, Tezuka K, Amann E. Osteoblast-specific factor 2: cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I. Biochem J. 1993;294(Pt1):271–8. doi: 10.1042/bj2940271. - DOI - PMC - PubMed
    1. Yoshiba N, Yoshiba K, Hosoya A, Saito M, Yokoi T, Okiji T, Amizuka N, Ozawa H. Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse mandible development. Cell Tissue Res. 2007;330(1):133–45. doi: 10.1007/s00441-007-0439-x. - DOI - PubMed

LinkOut - more resources