|Table of Contents|

Hypoxia-inducible factor-1A up-regulates HMGN5 expression and promotes distant metastasis of osteosarcoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2019 04
Page:
556-560
Research Field:
Publishing date:

Info

Title:
Hypoxia-inducible factor-1A up-regulates HMGN5 expression and promotes distant metastasis of osteosarcoma
Author(s):
Zhang KeXu EnjieYin JiaMa XiaoZhou Xuhui
The Fourth Department of Spine,Shanghai Changzheng Hospital,Shanghai 200003,China.
Keywords:
HIF-1AHMGN5osteosarcomametastasismolecular mechanism
PACS:
R738.1
DOI:
10.3969/j.issn.1672-4992.2019.04.004
Abstract:
Objective:To explore the molecular mechanism of the effect of hypoxia-inducible factor-1A (HIF-1A) on promoting the expression of high-mobility group nucleosome-binding domain 5 (HMGN5) and further affecting the distant metastasis of osteosarcoma.Methods:Lentivirus infection was used to overexpress and knock down the expression of target gene in osteosarcoma cell line U2OS.We obtained a total of 3 groups of cells,namely the virus infection control group,HIF-1A overexpression group,HIF-1A overexpression and HMGN5 knockdown group.We examined the ability of osteosarcoma cells to migrate and invade by wound healing assay and Transwell invasion experiment.To use PROMO software to predict the transcription factor of HMGN5 and fluorescence quantitative PCR to identify it.Western-blot was used to detect the expression of HIF-1A,HMGN5 and tumor metastasis-related pathway members.Results:Overexpression of HIF-1A up-regulated the expression of transcription factor GATA1 and promoted the expression of HMGN5.The higher expression of HMGN5 upregulated the expression of MMP-2 and MMP-9 through the c-jun pathway,and finally promoted the migration and invasion of osteosarcoma cells.Conclusion:The up-regulation of HMGN5 expression is an important downstream factor in the promotion of distant metastasis of osteosarcoma by HIF-1A,and it has important clinical practical significance in the selection of therapeutic targets for osteosarcoma.

References:

[1] ESMO/European Sarcoma Network Working Group.Bone sarcomas:ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up[J].Ann Oncol,2014,25(Suppl 3):iii113-123.
[2] Jo VY,Fletcher CD.WHO classification of soft tissue tumours:An update based on the 2013 (4th) edition[J].Pathology,2014,46(2):95-104.
[3] Gordon N,Kleinerman ES.Aerosol therapy for the treatment of osteosarcoma lung metastases:Targeting the Fas/FasL pathway and rationale for the use of gemcitabine[J].J Aerosol Med Pulm Drug Deliv,2010,23(4):189-196.
[4] Reed DR,Hayashi M,Wagner L,et al.Treatment pathway of bone sarcoma in children,adolescents,and young adults[J].Cancer,2017,123(12):2206-2218.
[5] Wagner MJ,Livingston JA,Patel SR,et al.Chemotherapy for bone sarcoma in adults[J].J Oncol Pract,2016,12(3):208-216.
[6] Palmerini E,Jones RL,Marchesi E,et al.Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone[J].BMC Cancer,2016,16:280.
[7] Podda MG,Luksch R,Puma N,et al.Oral etoposide in relapsed or refractory Ewing sarcoma:A monoinstitutional experience in children and adolescents[J].Tumori,2016,102(1):84-88.
[8]Nakano K,Takahashi S.Current molecular targeted therapies for bone and soft tissue sarcomas[J].Int J Mol Sci,2018,19(3):E739.
[9] Wittig JC,Bickels J,Priebat D,et al.Osteosarcoma:A multidisciplinary approach to diagnosis and treatment[J].Am Fam Physician,2002,65(6):1123-1132.
[10] Tsuchiya H,Kanazawa Y,Abdel-Wanis ME,et al.Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma:The Japanese Musculoskeletal Oncology Group study[J].J Clin Oncol,2002,20(16):3470-3477.
[11] Shi Z,Tang R,Wu D,et al.Research advances in HMGN5 and cancer[J].Tumour Biol,2016,37(2):1531-1539.
[12]Wei P,Qiao B,Li Q,et al.MicroRNA-340 suppresses tumorigenic potential of prostate cancer cells by targeting high-mobility group nucleosome-binding domain 5[J].DNA Cell Biol,2016,35(1):33-43.
[13]Gan Y,Tan J,Yang J,et al.Knockdown of HMGN5 suppresses the viability and invasion of human urothelial bladder cancer 5637 cells in vitro and in vivo[J].Med Oncol,2015,32(4):1-9.
[14] Wu J,Wang J.HMGN5 expression in bladder cancer tissue and its role on prognosis[J].Eur Rev Med Pharmacol Sci,2018,22(4):970-975.
[15]Wei X,Yu L,Kong X,et al.miR-488 inhibits cell growth and metastasis in renal cell carcinoma by targeting HMGN5[J].Onco Targets Ther,2018,11:2205-2216.
[16]Weng M,Song F,Chen J,et al.The high-mobility group nucleosome-binding domain 5 is highly expressed in breast cancer and promotes the proliferation and invasion of breast cancer cells[J].Tumour Biol,2015,36(2):959-966.
[17]Zhou X,Yuan B,Yuan W,et al.The expression and clinical significance of high mobility group nucleosome binding domain 5 in human osteosarcoma[J].Tumour Biol,2014,35(7):6539-6547.

Memo

Memo:
上海市科学技术委员会科研计划项目(编号:16140901800)
Last Update: 1900-01-01