Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma

Abstract Objective Circular RNAs (circRNAs), pivotal in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), remain a significant point of investigation for potential therapeutic interventions. Our research was driven by the objective to decipher the roles and underlying mechanisms of...

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Main Authors: ZeJun Zhou, Fang Xu, Tao Zhang
Format: Article
Language:English
Published: Springer 2024-04-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-024-00941-1
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author ZeJun Zhou
Fang Xu
Tao Zhang
author_facet ZeJun Zhou
Fang Xu
Tao Zhang
author_sort ZeJun Zhou
collection DOAJ
description Abstract Objective Circular RNAs (circRNAs), pivotal in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), remain a significant point of investigation for potential therapeutic interventions. Our research was driven by the objective to decipher the roles and underlying mechanisms of hsa_circ_0044569 (circCOL1A1) in governing the malignant phenotypes and the Warburg effect in NPC. Methods We systematically collected samples from NPC tissues and normal nasopharyngeal epithelial counterparts. The expression levels of circCOL1A1, microRNA-370-5p (miR-370-5p), and prothymosin alpha (PTMA) were quantitatively determined using quantitative polymerase chain reaction (qPCR) and Western blotting. Transfections in NPC cell lines were conducted using small interfering RNAs (siRNAs) or vectors carrying the pcDNA 3.1 construct for overexpression studies. We interrogated the circCOL1A1/miR-370-5p/PTMA axis's role in cellular functions through a series of assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide for cell viability, colony formation for growth, Transwell assays for migration and invasion, and Western blotting for protein expression profiling. To elucidate the molecular interactions, we employed luciferase reporter assays and RNA immunoprecipitation techniques. Results Our investigations revealed that circCOL1A1 was a stable circRNA, highly expressed in both NPC tissues and derived cell lines. A correlation analysis with clinical pathological features demonstrated a significant association between circCOL1A1 expression, lymph node metastasis, and the tumor node metastasis staging system of NPC. Functionally, silencing circCOL1A1 led to substantial suppression of cell proliferation, migration, invasion, and metabolic alterations characteristic of the Warburg effect in NPC cells. At the molecular level, circCOL1A1 appeared to modulate PTMA expression by acting as a competitive endogenous RNA or 'sponge' for miR-370-5p, which in turn promoted the malignant characteristics of NPC cells. Conclusion To conclude, our findings delineate that circCOL1A1 exerts its oncogenic influence in NPC through the modulation of the miR-370-5p/PTMA signaling axis.
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spelling doaj.art-40a14bb791014b1fb8a87255475b7cf52024-04-21T11:22:49ZengSpringerDiscover Oncology2730-60112024-04-0115111610.1007/s12672-024-00941-1Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinomaZeJun Zhou0Fang Xu1Tao Zhang2Department of Otolaryngology, The First Affiliated Hospital of Jinan UniversityHealth Management Center, The First Affiliated Hospital of Jinan UniversityDepartment of Otolaryngology, The First Affiliated Hospital of Jinan UniversityAbstract Objective Circular RNAs (circRNAs), pivotal in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), remain a significant point of investigation for potential therapeutic interventions. Our research was driven by the objective to decipher the roles and underlying mechanisms of hsa_circ_0044569 (circCOL1A1) in governing the malignant phenotypes and the Warburg effect in NPC. Methods We systematically collected samples from NPC tissues and normal nasopharyngeal epithelial counterparts. The expression levels of circCOL1A1, microRNA-370-5p (miR-370-5p), and prothymosin alpha (PTMA) were quantitatively determined using quantitative polymerase chain reaction (qPCR) and Western blotting. Transfections in NPC cell lines were conducted using small interfering RNAs (siRNAs) or vectors carrying the pcDNA 3.1 construct for overexpression studies. We interrogated the circCOL1A1/miR-370-5p/PTMA axis's role in cellular functions through a series of assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide for cell viability, colony formation for growth, Transwell assays for migration and invasion, and Western blotting for protein expression profiling. To elucidate the molecular interactions, we employed luciferase reporter assays and RNA immunoprecipitation techniques. Results Our investigations revealed that circCOL1A1 was a stable circRNA, highly expressed in both NPC tissues and derived cell lines. A correlation analysis with clinical pathological features demonstrated a significant association between circCOL1A1 expression, lymph node metastasis, and the tumor node metastasis staging system of NPC. Functionally, silencing circCOL1A1 led to substantial suppression of cell proliferation, migration, invasion, and metabolic alterations characteristic of the Warburg effect in NPC cells. At the molecular level, circCOL1A1 appeared to modulate PTMA expression by acting as a competitive endogenous RNA or 'sponge' for miR-370-5p, which in turn promoted the malignant characteristics of NPC cells. Conclusion To conclude, our findings delineate that circCOL1A1 exerts its oncogenic influence in NPC through the modulation of the miR-370-5p/PTMA signaling axis.https://doi.org/10.1007/s12672-024-00941-1Nasopharyngeal carcinomacircCOL1A1miR-370-5pPTMAWarburg effect
spellingShingle ZeJun Zhou
Fang Xu
Tao Zhang
Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma
Discover Oncology
Nasopharyngeal carcinoma
circCOL1A1
miR-370-5p
PTMA
Warburg effect
title Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma
title_full Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma
title_fullStr Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma
title_full_unstemmed Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma
title_short Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma
title_sort circular rna col1a1 promotes warburg effect and tumor growth in nasopharyngeal carcinoma
topic Nasopharyngeal carcinoma
circCOL1A1
miR-370-5p
PTMA
Warburg effect
url https://doi.org/10.1007/s12672-024-00941-1
work_keys_str_mv AT zejunzhou circularrnacol1a1promoteswarburgeffectandtumorgrowthinnasopharyngealcarcinoma
AT fangxu circularrnacol1a1promoteswarburgeffectandtumorgrowthinnasopharyngealcarcinoma
AT taozhang circularrnacol1a1promoteswarburgeffectandtumorgrowthinnasopharyngealcarcinoma