Open Access

ARTICLE

LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis

by CHAOQUN WANG¹, TING ZHANG², CHAOHE ZHANG^3,*

1 Department of Gynecology, Aviation General Hospital, Beijing, 100020, China
2 Department of Burn and Skin Surgery, First Affiliated Hospital of Air Force Military Medical University, Xi’an, 710032, China
3 Department of Oncology and Hematology, Second Hospital of Jilin University, Changchun, 130000, China

* Corresponding Author: CHAOHE ZHANG. Email:

Oncology Research 2024, 32(12), 1867-1879. https://doi.org/10.32604/or.2024.044547

Received 02 August 2023; Accepted 10 July 2024; Issue published 13 November 2024

Abstract

Background: Drug resistance is the main factor contributing to cancer recurrence and poor prognosis. Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy. In our study, the role of long non-coding RNA (lncRNA) AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells. Methods: Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method. The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis. The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay. Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium (MTT), soft agar, and colony formation experiments. Cell cycle and apoptosis were detected by flow cytometry. Results: Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis. Besides, patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group. AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells. In addition, AFAP1-AS1 mediated epidermal growth factor receptor (EGFR) expression by serving as a molecular sponge for microRNA-7a-5p (miR-7-5p). This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance. Conclusions: In general, the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer, providing potential targets for the management of cervical cancer.

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Supplementary Material

Supplementary Material File

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