Collagen modifying enzyme P4HA1 is overexpressed and plays a role in lung adenocarcinoma
| Autor: | Mick D. Edmonds, David G. Beer, Darshan S. Chandrashekar, Upender Manne, Sooryanarayana Varambally, Balabhadrapatruni V. S. K. Chakravarthi, Mackenzie L Davenport, Sumit Agarwal, Guoan Chen, Alyncia D. Robinson |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Survival 03 medical and health sciences 0302 clinical medicine Invasion microRNA Gene expression Medicine Lung cancer RC254-282 Original Research Gene knockdown Lung business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Lung Adenocarcinoma MicroRNA respiratory system medicine.disease Phenotype respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Adenocarcinoma Biomarker (medicine) business Collagen prolyl 4-hydroxylases |
| Zdroj: | Translational Oncology Translational Oncology, Vol 14, Iss 8, Pp 101128-(2021) |
| ISSN: | 1936-5233 |
| Popis: | Highlights • Lung cancer is the leading cause of cancer-related deaths globally. • Collagen-modifying enzyme P4HA1 is highly overexpressed in NSCLC. • Our study suggests that collagen-modifying enzymes play an important role in lung cancer aggressiveness. • Novel inhibitors for druggable targets in these pathways are imperative. Lung cancer is the leading cause of cancer-related deaths globally and is histologically defined as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), with the latter accounting for 80% of all lung cancers. The 5-year overall survival rate for lung cancer patients is low as it is often discovered at advanced stages when potential cure by surgical resection is no longer an option. To identify a biomarker and target for lung cancer, we performed analysis of multiple datasets of lung cancer gene expression data. Our analyses indicated that the collagen-modifying enzyme Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is overexpressed in NSCLC. Furthermore, our investigation found that overexpression of enzymes involved in this pathway predicts poor outcome for patients with lung adenocarcinoma. Our functional studies using knockdown strategies in lung cancer cell lines in vitro indicated that P4HA1 is critical for lung cancer growth, migration, and invasion. Additionally, diethyl pythiDC (PythiDC), a small molecule inhibitor, decreased the malignant phenotypes of lung cancer cells. Moreover, we found that miR-124 regulates and targets P4HA1 in lung cancer cells. Thus, our study suggests that collagen-modifying enzymes play an important role in lung cancer aggressiveness. Furthermore, our studies showed that P4HA1 is required for lung cancer cell growth and invasion, suggesting its potential as a valid therapeutic target in lung adenocarcinoma. |
| Databáze: | OpenAIRE |
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