HOXA5 Is Recognized As a Prognostic-Related Biomarker and Promotes Glioma Progression Through Affecting Cell Cycle

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Sep 6

PMID 34485110

Citations 5

Authors

Fengqin Ding

Ping Chen

Pengfei Bie

Wenhua Piao

Quan Cheng

Affiliations

Soon will be listed here.

Abstract

Glioma is malignant tumor derives from glial cells in the central nervous system. High-grade glioma shows aggressive growth pattern, and conventional treatments, such as surgical removal and chemo-radiotherapy, archive limitation in the interference of this process. In this work, HOXA5, from the HOX family, was identified as a glioma cell proliferation-associated factor by investigating its feature in the TCGA and CGGA data set. High HOXA5 expression samples contain unfavorable clinical features of glioma, including IDH wild type, un-methylated MGMT status, non-codeletion 1p19q status, malignant molecular subtype. Survival analysis indicates that high HOXA5 expression samples are associated with worse clinical outcome. The CNVs and SNPs profile difference further confirmed the enrichment of glioma aggressive related biomarkers. In the meantime, the activation of DNA damage repair-related pathways and TP53-related pathways is also related to HOXA5 expression. In cell lines, U87MG and U251, by interfering HOXA5 expression significantly inhibit glioma progression and apoptosis, and cell cycle is arrested at the G2/M phase. Collectively, increased HOXA5 expression can promote glioma progression affecting glioma cell proliferation.

Citing Articles

Super-enhancer-driven SLCO4A1-AS1 is a new biomarker and a promising therapeutic target in glioblastoma.

Wu Y, Li F, Yang C, Zhang X, Xue Z, Sun Y Sci Rep. 2025; 15(1):954.

PMID: 39762261 PMC: 11704019. DOI: 10.1038/s41598-024-82109-z.

Comprehensive analysis of HOX family genes in endometrial cancer.

Zhao L, Lou W, Zhang Y, Han Y, Zhang W Transl Cancer Res. 2024; 12(12):3728-3743.

PMID: 38192984 PMC: 10774039. DOI: 10.21037/tcr-23-2146.

The Transcription Factor : Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction.

Parrillo L, Spinelli R, Longo M, Zatterale F, Santamaria G, Leone A Cells. 2023; 12(16).

PMID: 37626900 PMC: 10453582. DOI: 10.3390/cells12162090.

Identification of Gender- and Subtype-Specific Gene Expression Associated with Patient Survival in Low-Grade and Anaplastic Glioma in Connection with Steroid Signaling.

Hirtz A, Lebourdais N, Thomassin M, Rech F, Dumond H, Dubois-Pot-Schneider H Cancers (Basel). 2022; 14(17).

PMID: 36077653 PMC: 9454517. DOI: 10.3390/cancers14174114.

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.

Rocchi A, Wollebo H, Khalili K Int J Mol Sci. 2022; 23(17).

PMID: 36077131 PMC: 9456419. DOI: 10.3390/ijms23179734.

References

Ellis J, Canoll P, McCormick 2nd P, Feldstein N, Anderson R, Angevine P . Platelet-derived growth factor receptor (PDGFR) expression in primary spinal cord gliomas. J Neurooncol. 2011; 106(2):235-42. PMC: 3869991. DOI: 10.1007/s11060-011-0666-6. View

Xu H, Zong H, Ma C, Ming X, Shang M, Li K . Epidermal growth factor receptor in glioblastoma. Oncol Lett. 2017; 14(1):512-516. PMC: 5494611. DOI: 10.3892/ol.2017.6221. View

Teo W, Merino V, Cho S, Korangath P, Liang X, Wu R . HOXA5 determines cell fate transition and impedes tumor initiation and progression in breast cancer through regulation of E-cadherin and CD24. Oncogene. 2016; 35(42):5539-5551. PMC: 5073039. DOI: 10.1038/onc.2016.95. View

Boyarskikh U, Gulyaeva L, Avdalyan A, Kechin A, Khrapov E, Lazareva D . Spectrum of Mutations in BRCA1/2 Associated High-Grade Serous Ovarian Cancer. Front Oncol. 2020; 10:1103. PMC: 7378769. DOI: 10.3389/fonc.2020.01103. View

Zhang H, Zhou Y, Cheng Q, Dai Z, Wang Z, Liu F . PDIA3 correlates with clinical malignant features and immune signature in human gliomas. Aging (Albany NY). 2020; 12(15):15392-15413. PMC: 7467394. DOI: 10.18632/aging.103601. View

Gao F, Liu W, Guo Q, Bai Y, Yang H, Chen H . Physcion blocks cell cycle and induces apoptosis in human B cell precursor acute lymphoblastic leukemia cells by downregulating HOXA5. Biomed Pharmacother. 2017; 94:850-857. DOI: 10.1016/j.biopha.2017.07.149. View

Li J, Ye M, Zhou C . Expression Profile and Prognostic Values of Family Members in Laryngeal Squamous Cell Cancer. Front Oncol. 2020; 10:368. PMC: 7136465. DOI: 10.3389/fonc.2020.00368. View

Zhang H, Wang R, Yu Y, Liu J, Luo T, Fan F . Glioblastoma Treatment Modalities besides Surgery. J Cancer. 2019; 10(20):4793-4806. PMC: 6775524. DOI: 10.7150/jca.32475. View

Hou X, Snarski P, Higashi Y, Yoshida T, Jurkevich A, Delafontaine P . Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death. FASEB J. 2017; 31(7):3179-3192. PMC: 5471514. DOI: 10.1096/fj.201601082R. View

10.

Jeannotte L, Gotti F, Landry-Truchon K . Hoxa5: A Key Player in Development and Disease. J Dev Biol. 2018; 4(2). PMC: 5831783. DOI: 10.3390/jdb4020013. View

11.

Zhang H, He J, Dai Z, Wang Z, Liang X, He F . PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas. Front Immunol. 2021; 12:628966. PMC: 7921737. DOI: 10.3389/fimmu.2021.628966. View

12.

Lee D, Forscher C, Di Vizio D, Koeffler H . Induction of p53-independent apoptosis by ectopic expression of HOXA5 in human liposarcomas. Sci Rep. 2015; 5:12580. PMC: 4518222. DOI: 10.1038/srep12580. View

13.

Wang X, Chen J, Liu J, You C, Liu Y, Mao Q . Gain of function of mutant TP53 in glioblastoma: prognosis and response to temozolomide. Ann Surg Oncol. 2013; 21(4):1337-44. DOI: 10.1245/s10434-013-3380-0. View

14.

Li D, Bai Y, Feng Z, Li W, Yang C, Guo Y . Study of Promoter Methylation Patterns of HOXA2, HOXA5, and HOXA6 and Its Clinicopathological Characteristics in Colorectal Cancer. Front Oncol. 2019; 9:394. PMC: 6536611. DOI: 10.3389/fonc.2019.00394. View

15.

Duan X, Liu D, Wang Y, Chen Z . Circular RNA hsa_circ_0074362 Promotes Glioma Cell Proliferation, Migration, and Invasion by Attenuating the Inhibition of miR-1236-3p on HOXB7 Expression. DNA Cell Biol. 2018; 37(11):917-924. DOI: 10.1089/dna.2018.4311. View

16.

Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M . Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1):98-110. PMC: 2818769. DOI: 10.1016/j.ccr.2009.12.020. View

17.

Chen H, Chung S, Sukumar S . HOXA5-induced apoptosis in breast cancer cells is mediated by caspases 2 and 8. Mol Cell Biol. 2004; 24(2):924-35. PMC: 343791. DOI: 10.1128/MCB.24.2.924-935.2004. View

18.

Li B, Huang Q, Wei G . The Role of HOX Transcription Factors in Cancer Predisposition and Progression. Cancers (Basel). 2019; 11(4). PMC: 6520925. DOI: 10.3390/cancers11040528. View

19.

Zhang H, Zhou Y, Cui B, Liu Z, Shen H . Novel insights into astrocyte-mediated signaling of proliferation, invasion and tumor immune microenvironment in glioblastoma. Biomed Pharmacother. 2020; 126:110086. DOI: 10.1016/j.biopha.2020.110086. View

20.

Zhang H, Fan F, Yu Y, Wang Z, Liu F, Dai Z . Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas. J Transl Med. 2020; 18(1):305. PMC: 7409670. DOI: 10.1186/s12967-020-02460-3. View