HOXA1 is Overexpressed in Oral Squamous Cell Carcinomas and Its Expression is Correlated with Poor Prognosis

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2012 Apr 14

PMID 22498108

Citations 45

Authors

Carolina Cavalcante Bitu

Maria Fernanda de Souza Setubal Destro

Manoela Carrera

Sabrina Daniela da Silva

Edgard Graner

Luiz Paulo Kowalski

Fernando Augusto Soares

Ricardo D Coletta

Affiliations

Soon will be listed here.

Abstract

Background: HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer.

Methods: In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression.

Results: We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026).

Conclusion: Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1 expression might be helpful as a prognostic marker for patients with OSCC.

Citing Articles

3'UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma.

Pereira Sorroche B, Miranda K, Beltrami C, Arantes L, Kowalski L, Marchi F Cancers (Basel). 2024; 16(5).

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Role of HOXA1-4 in the development of genetic and malignant diseases.

Wang L, Sun H, Cao L, Wang J Biomark Res. 2024; 12(1):18.

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MicroRNA-495: a therapeutic and diagnostic tumor marker.

Maharati A, Tolue Ghasaban F, Akhlaghipour I, Taghehchian N, Zangouei A, Moghbeli M J Mol Histol. 2023; 54(6):559-578.

PMID: 37759132 DOI: 10.1007/s10735-023-10159-0.

HOXA1 participates in VSMC-to-macrophage-like cell transformation via regulation of NF-κB p65 and KLF4: a potential mechanism of atherosclerosis pathogenesis.

Han Z, Hu H, Yin M, Lin Y, Yan Y, Han P Mol Med. 2023; 29(1):104.

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HOXA1 is a radioresistance marker in multiple cancer types.

He L, Liang M, Guo W, Liu J, Yu Y Front Oncol. 2022; 12:965427.

PMID: 36119466 PMC: 9478604. DOI: 10.3389/fonc.2022.965427.

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