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Molecular Cancer

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Open Access 01-12-2024 | Osimertinib | Research

circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)

Authors: Yi-fang Tang, Zheng-hua Liu, Lei-yi Zhang, Sheng-hao Shi, Shun Xu, Jin-An Ma, Chun-Hong Hu, Fang-wen Zou

Published in: Molecular Cancer | Issue 1/2024

Abstract

Background

Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC.

Methods

Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis.

Results

The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance.

Conclusions

Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Graphical Abstract

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Title: circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)
Authors: Yi-fang Tang
Zheng-hua Liu
Lei-yi Zhang
Sheng-hao Shi
Shun Xu
Jin-An Ma
Chun-Hong Hu
Fang-wen Zou
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Osimertinib
NSCLC
NSCLC
Published in: Molecular Cancer / Issue 1/2024
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-024-01998-w

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Abstract

Background

Methods

Results

Conclusions

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