CircCOL1A1 promotes proliferation, migration, and invasion of colorectal cancer (CRC) cells and glutamine metabolism via GLS1 up-regulation by sponging miR-214-3p

Sep 21, 2026

Circular RNAs are abundant noncoding RNAs with broad roles in disease, yet the specific function of individual circRNAs in colorectal cancer (CRC) remains incompletely defined. This study quantified circRNAs and mRNA in CRC cell lines and tissues, then evaluated circCOL1A1 knockdown effects in vitro and in vivo using proliferation, clonogenic, invasion, and xenograft assays. Mechanistic links were analyzed with luciferase reporter assays, Western blotting, RNA immunoprecipitation, and immunohistochemistry. circCOL1A1 was elevated in CRC and associated with TNM stage and metastasis. Knockdown reduced CRC invasion, migration, proliferation, and tumor growth, acting as a sponge for miR-214-3p to increase GLS1 and drive glutamine metabolism. The findings implicate the circCOL1A1/miR-214-3p/GLS1 axis as an oncogenic driver and therapeutic target.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

CircRNAs as biomarkers and regulators in cancer

CRC clinical challenges and need for early detection

circRNA–miRNA axis in cancer biology

Journal of Cancer Research and Clinical Oncology (2024) 150:211 [https://doi.org/10.1007/s00432-024-05736-z](https://doi.org/10.1007/s00432-024-05736-z) CircCOL1A1 promotes proliferation, migration, and invasion of colorectal cancer (CRC) cells and glutamine metabolism through GLS1 up‑regulation by sponging miR‑214‑3p Jia Liu1,2 · Xianbo Zhang2 · MeijianYang2 · Xianghong Zhang3 Received: 7 December 2023 / Accepted: 31 March 2024 / Published online: 25 April 2024 © The Author(s) 2024 Abstract Background Circular ribose nucleic acids (circRNAs), an abundant type of noncoding RNAs, are widely expressed in eukaryotic cells and exert a significant impact on the initiation and progression of various disorders, including different types of cancer. However, the specific role of various circRNAs in colorectal cancer (CRC) pathology is still not fully understood. Methods The initial step involved the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of circRNAs and messenger RNA (mRNA) in CRC cell lines and tissues. Subsequently, functional analyses of circCOL1A1 knockdown were conducted in vitro and in vivo through cell counting kit (CCK)-8, colony formation and transwell assays, as well as xenograft mouse model of tumor formation. Molecular expression and interactions were investigated using luciferase reporter assays, Western blot analysis, RNA immunoprecipitation (RIP), and immunohistochemical staining. Results The RT-qPCR results revealed elevated levels ofcircCOL1A1 expressions in CRC tissues and cell lines as compared to the normal counterparts. In addition, circCOL1A1 expression level was found to be correlated with TNM stage, lymph node metastases, distant metastases, and invasion. Knockdown of circCOL1A1 resulted in impaired invasion, migration, and proliferation of CRC cells, and suppressed tumor generation in the animal model. We further demonstrated that circCOL1A1 could act as a sponge for miR-214-3p, suppressing miR-214-3p activity and leading to the upregulation of GLS1 protein to promote glutamine metabolism. Conclusion These findings suggest that circCOL1A1 functions as an oncogenic molecule to promote CRC progression via miR-214-3p/GLS1 axis, hinting on the potential of circCOL1A1 as a therapeutic target for CRC. Keywords Colorectal cancer · circCOL1A1 · miR-214-3p/GLS1 axis * Xianghong Zhang [zhangxianghong3210@163.com](zhangxianghong3210@163.com) 1 Oncology Teaching and Research Office, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang City 050017, Hebei, China 2 Second Department of Oncology, Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang City 050051, Hebei Province, China 3 Department of Pathology, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang City 050000, Hebei, China Introduction Colorectal cancer (CRC) has become the second leading cause of cancer-related deaths and the third most prevalent cancer worldwide, resulting in a significant number of annual fatalities (Sung et al. 2020) . Despite numerous advancements in diagnosing and treating CRC, patient outcomes are still grim due to late detection, drug resistance, high recurrence rates, and metastasis (Dienstmannet al. 2017) . Early detection is crucial for successful intervention, but the current methods have limitations. Thereis a lack of reliable noninvasive test for CRC early detection, and invasive colonoscopy screening can also generate false positive and negative results (Miller Wilson et al. 2023 ; Smith et al. 2021) . The course of treatment for CRC patients depends on the stage and specific characteristics of the cancer, which include localized treatments (surgery, ablation and embolization, radiation therapy) and systemic treatments (chemotherapy, taregted therapy and immunotherapy) (Adebayo et al. 2023) . When considering the limitations of cytotoxic chemotherapy, targeted therapies

FAQs

What is the main biological role of circCOL1A1 in CRC according to the study?

circCOL1A1 is upregulated in CRC and promotes invasion, migration, and proliferation of CRC cells, as well as tumor formation in vivo.

How did the researchers determine circCOL1A1 expression and its association with clinical features?

They used RT-qPCR to measure circCOL1A1 in CRC tissues and cell lines, and correlated expression with TNM stage, lymph node metastases, distant metastases, and invasion.

What mechanism links circCOL1A1 to glutamine metabolism?

circCOL1A1 functions as a sponge for miR-214-3p, suppressing miR-214-3p activity and leading to GLS1 upregulation, which promotes glutamine metabolism.

Sep 21, 2026

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