Open Access

ARTICLE

Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

JIA SHAO^1,2, CAN ZHANG², YAONAN TANG², AIQIN HE², WEIPEI ZHU^1,*

1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
2 Department of Gynecology Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226361, China

* Corresponding Author: WEIPEI ZHU. Email:

(This article belongs to the Special Issue: MicroRNA as Biomarkers for Disease Diagnosis and Progression)

BIOCELL 2024, 48(4), 571-580. https://doi.org/10.32604/biocell.2024.049092

Received 27 December 2023; Accepted 26 February 2024; Issue published 09 April 2024

Abstract

Objective: Previous studies indicated that aberrant circular RNA (circRNA) expression affects gene expression regulatory networks, leading to the aberrant activation of tumor pathways and promoting tumor cell growth. However, the expression, clinical significance, and effects on cell propagation, invasion, and dissemination of circRNA_001896 in cervical cancer (CC) tissues remain unclear. Methods: The Gene Expression Omnibus (GEO) datasets (GSE113696 and GSE102686) were used to examine differential circRNA expression in CC and adjacent tissues. The expression of circRNA_001896 was detected in 72 CC patients using fluorescence quantitative PCR. Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis. The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8 (CCK-8) test, clonogenic, 3D sphere formation, and in vivo tumorigenesis assays. Results: Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs, including circRNA_001896, in CC tissues. Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA. High expression of circRNA_001896 was considerably associated with lymph node metastasis, International Federation of Gynecologists and Obstetricians (FIGO) stage, tumor diameter, and survival period in CC patients. Proportional hazards model (COX) univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’ prognosis. Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth, colony formation, and 3D sphere-forming ability. In vivo, tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells. Conclusion: CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis, FIGO stage, tumor size, and survival period in patients. Moreover, downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells. Therefore, circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

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Supplementary Material

Supplementary Material File

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