1. circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).
- Author
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Tang YF, Liu ZH, Zhang LY, Shi SH, Xu S, Ma JA, Hu CH, and Zou FW
- Subjects
- Humans, Cell Line, Tumor, Animals, Mice, Apoptosis, Cell Movement genetics, Xenograft Model Antitumor Assays, Male, Female, Indoles, Pyrimidines, MicroRNAs genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung metabolism, Receptor, IGF Type 1 genetics, Receptor, IGF Type 1 metabolism, Drug Resistance, Neoplasm genetics, Acrylamides pharmacology, RNA, Circular genetics, Lung Neoplasms genetics, Lung Neoplasms pathology, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Aniline Compounds pharmacology, Gene Expression Regulation, Neoplastic, Cell Proliferation, Signal Transduction
- 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., (© 2024. The Author(s).)
- Published
- 2024
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