Open Access

ARTICLE

COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway

LIANG HE^1,2, WEI HAN^1,3, KAI YUE¹, XUDONG WANG^1,*

1 Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer (Tianjin), Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center for Cancer, Tianjin, 300060, China
2 Department of Thyroid & Breast Surgery, Luoyang Central Hospital, Luoyang, 471000, China
3 Department of Otorhinolaryngological Surgery, Zhengzhou Central Hospital, Zhengzhou, 450000, China

* Corresponding Author: XUDONG WANG. Email:

Oncology Research 2024, 32(9), 1467-1478. https://doi.org/10.32604/or.2024.047382

Received 03 November 2023; Accepted 15 March 2024; Issue published 23 August 2024

Abstract

Objectives: Thyroid cancer (THCA) is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide. And the number of patients dying from THCA has also gradually risen because the incidence continues to increase, so the mechanisms related to effective targets is necessary to improve the survival. This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer (THCA) cell proliferation and the associated pathways. Methods: Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development. COL4A2 expression in THCA tissues was analyzed using immunohistochemistry, and survival information was determined via Kaplan‒Meier curves. The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses. Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity, respectively. Downstream of COL4A2 was identified by Gene set enrichment analysis (GSEA). The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model. Results: Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2. THCA patients with high COL4A2 expression had shorter recurrence-free survival. Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity. The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines. The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival. Conclusions: COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

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