Top

Journal of Orthopaedic Surgery and Research

Published in:

01-12-2020 | osteosarcoma | Research article

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Authors: Hai-ping Zhang, Zi-liang Yu, Bing-bing Wu, Fa-rui Sun

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2020

Abstract

Background

This article reports the effects of proenkephalin (PENK) on osteosarcoma (OS) cell migration.

Methods

A Gene Expression Omnibus (GEO) dataset was used to identify differentially expressed genes (DEGs) in OS tumor samples and normal human osteoblasts. Tumor tissue and adjacent normal tissue were collected from 40 OS patients. MG63 cells were transfected with si-PENK. Transwell migration assays and wound healing assays were performed to compare the effect of PENK on migration. Moreover, LY294002 was used to identify the potential mechanism. Gene expression was examined via qRT-PCR and Western blotting.

Results

Bioinformatic analysis revealed that PENK was downregulated in OS tumor samples compared with normal human osteoblasts. Moreover, PENK was identified as the hub gene of the DEGs. The PI3K/Akt signaling pathway was significantly enriched in the DEGs. Moreover, PENK was downregulated in OS and MG63 cells compared with the corresponding control cells. Silencing PENK promoted MG63 cell migration; however, treatment with LY294002 partially attenuated PENK silencing-induced OS cell migration.

Conclusion

PENK inhibits OS cell migration by activating the PI3K/Akt signaling pathway.

Rickel K, Fang F, Tao J. Molecular genetics of osteosarcoma. Bone. 2017;102:69–79. https://doi.org/10.1016/j.bone.2016.10.017.CrossRefPubMed

Zha Z, Han Q, Liu W, et al. lncRNA GAS8-AS1 downregulates lncRNA UCA1 to inhibit osteosarcoma cell migration and invasion. J Orthop Surg Res. 2020;15:38. https://doi.org/10.1186/s13018-020-1550-x.CrossRefPubMedPubMedCentral

Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end Results program. Cancer. 2009;115:1531–43. https://doi.org/10.1002/cncr.24121.CrossRefPubMed

Wu B, Xing C, Tao J. Upregulation of microRNA-23b-3p induced by farnesoid X receptor regulates the proliferation and apoptosis of osteosarcoma cells. 2019, 14: 398 DOI: 10.1186/s13018-019-1404-6.

Goryn T, Pienkowski A, Szostakowski B, et al. Functional outcome of surgical treatment of adults with extremity osteosarcoma after megaprosthetic reconstruction-single-center experience. J Orthop Surg Res. 2019;14:346. https://doi.org/10.1186/s13018-019-1379-3.CrossRefPubMedPubMedCentral

Faisham WI, Mat Saad AZ, Alsaigh LN, et al. Prognostic factors and survival rate of osteosarcoma: a single-institution study. Asia-Pacific journal of clinical oncology. 2017;13:e104–10. https://doi.org/10.1111/ajco.12346.CrossRefPubMed

Han D, Wang M, Yu Z, et al. FGF5 promotes osteosarcoma cells proliferation via activating MAPK signaling pathway. Cancer Manag Res. 2019;11:6457–66. https://doi.org/10.2147/cmar.s200234.CrossRefPubMedPubMedCentral

Yang G, He F, Duan H, et al. lncRNA FLVCR-AS1 promotes osteosarcoma growth by targeting miR381-3p/CCND1. Onco Targets Ther. 2020;13:163–72. https://doi.org/10.2147/ott.s214813.CrossRefPubMedPubMedCentral

Wu H, Zhang J, Dai R, et al. Transferrin receptor-1 and VEGF are prognostic factors for osteosarcoma. J Orthop Surg Res. 2019;14:296. https://doi.org/10.1186/s13018-019-1301-z.CrossRefPubMedPubMedCentral

10.

Tegeder I, Geisslinger G. Opioids as modulators of cell death and survival--unraveling mechanisms and revealing new indications. Pharmacol Rev. 2004;56:351–69. https://doi.org/10.1124/pr.56.3.2.CrossRefPubMed

11.

Roperch JP, Incitti R, Forbin S, et al. Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer. BMC Cancer. 2013;13:566. https://doi.org/10.1186/1471-2407-13-566.CrossRefPubMedPubMedCentral

12.

Salhia B, Kiefer J, Ross JT, et al. Integrated genomic and epigenomic analysis of breast cancer brain metastasis. PLoS One. 2014;9:e85448. https://doi.org/10.1371/journal.pone.0085448.CrossRefPubMedPubMedCentral

13.

Zhang Y, Fang L, Zang Y, et al. Identification of core genes and key pathways via integrated analysis of gene expression and DNA methylation profiles in bladder cancer. Med Sci Monit, 2018, 24: 3024-3033 DOI: 10.12659/msm.909514.

14.

Wang X, Yin Z, Zhao Y, et al. Identifying potential prognostic biomarkers in head and neck cancer based on the analysis of microRNA expression profiles in TCGA database. Mol Med Rep. 2020. https://doi.org/10.3892/mmr.2020.10964.

15.

Zhou ZX, Chen XM, Zhang YQ, et al. Comprehensive analysis of long noncoding RNA and mRNA in five colorectal cancer tissues and five normal tissues. Biosci Rep. 2020. https://doi.org/10.1042/bsr20191139.

16.

Cao L, Chen Y, Zhang M, et al. Identification of hub genes and potential molecular mechanisms in gastric cancer by integrated bioinformatics analysis. PeerJ. 2018;6:e5180. https://doi.org/10.7717/peerj.5180.CrossRefPubMedPubMedCentral

17.

Zhao Z, Ma X, Ma J, et al. Naringin enhances endothelial progenitor cell (EPC) proliferation and tube formation capacity through the CXCL12/CXCR4/PI3K/Akt signaling pathway. Chem Biol Interact. 2018;286:45–51. https://doi.org/10.1016/j.cbi.2018.03.002.CrossRefPubMed

18.

Zagon IS, Smith JP, McLaughlin PJ. Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor. Int J Oncol. 1999;14:577–84. https://doi.org/10.3892/ijo.14.3.577.CrossRefPubMed

19.

Suzuki M, Chiwaki F, Sawada Y, et al. Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a cell growth-suppressive pathway in vivo. PLoS One. 2015;10:e0123407. https://doi.org/10.1371/journal.pone.0123407.CrossRefPubMedPubMedCentral

20.

Tang D, Lin T, Wang Y, et al. High expression of proenkephalin is associated with favorable outcomes in patients with gastrointestinal stromal tumors. Cancer Manag Res. 2019;11:6681–90. https://doi.org/10.2147/cmar.s202044.CrossRefPubMedPubMedCentral

21.

Aryee DN, Niedan S, Ban J, et al. Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing sarcoma. Br J Cancer. 2013;109:2696–704. https://doi.org/10.1038/bjc.2013.635.CrossRefPubMed

22.

Rosen H, Polakiewicz RD, Benzakine S, et al. Proenkephalin A in bone-derived cells. Proc Natl Acad Sci U S A. 1991;88:3705–9. https://doi.org/10.1073/pnas.88.9.3705.CrossRefPubMedPubMedCentral

23.

Zhang J, Yu XH, Yan YG, et al. PI3K/Akt signaling in osteosarcoma. Clin Chim Acta. 2015;444:182–92. https://doi.org/10.1016/j.cca.2014.12.041.CrossRefPubMed

24.

Scotlandi K, Picci P. Targeting insulin-like growth factor 1 receptor in sarcomas. Curr Opin Oncol. 2008;20:419–27. https://doi.org/10.1097/CCO.0b013e328302edab.CrossRefPubMed

25.

Lim HJ, Wang X, Crowe P, et al. Targeting the PI3K/PTEN/AKT/mTOR pathway in treatment of sarcoma cell lines. Anticancer Res, 2016, 36: 5765-5771 DOI: 10.21873/anticanres.11160.

26.

Zhang S, Li D, Jiao GJ, et al. miR-185 suppresses progression of Ewing’s sarcoma via inhibiting the PI3K/AKT and Wnt/β-catenin pathways. Onco Targets Ther. 2018;11:7967–77. https://doi.org/10.2147/ott.s167771.CrossRefPubMedPubMedCentral

Title: PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway
Authors: Hai-ping Zhang
Zi-liang Yu
Bing-bing Wu
Fa-rui Sun
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: osteosarcoma
Osteosarcoma
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2020
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-020-01679-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2020

Shoulder imbalance treated with scapuloplasty surgery in scoliosis patients: a clinical retrospective study

Association between plasma total homocysteine level within normal range and bone mineral density in adults

Comparison of targeted percutaneous vertebroplasty and traditional percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures in the elderly

Relationship between the inflammation/immune indexes and deep venous thrombosis (DVT) incidence rate following tibial plateau fractures

Propionibacterium acnes induces cartilaginous endplate degeneration by promoting MIF expression via the NF-κB pathway

Intrathecal versus local infiltration analgesia for pain control in total joint arthroplasty