Exosomal lncRNA FOXD3-AS1 upregulates ELAVL1 expression and activates PI3K/Akt pathway to enhance lung cancer cell proliferation, invasion, and 5-fluorouracil resistance
| Autor: | Guangxian Mao, Zhimin Mu, Da Wu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Antimetabolites Antineoplastic Lung Neoplasms animal structures Biophysics Adenocarcinoma of Lung Exosomes Biochemistry ELAV-Like Protein 1 Phosphatidylinositol 3-Kinases Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness RNA Small Interfering Lung cancer Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation A549 cell Phosphoinositide 3-kinase biology Akt/PKB signaling pathway Cell growth Forkhead Transcription Factors General Medicine Transfection Middle Aged respiratory system medicine.disease Small Cell Lung Carcinoma respiratory tract diseases Gene Expression Regulation Neoplastic A549 Cells Drug Resistance Neoplasm embryonic structures Carcinoma Squamous Cell biology.protein Cancer research Female RNA Long Noncoding Fluorouracil Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Acta Biochimica et Biophysica Sinica. 53:1484-1494 |
| ISSN: | 1672-9145 |
| DOI: | 10.1093/abbs/gmab129 |
| Popis: | Long non-coding RNA (lncRNA) FOXD3-AS1 expression is upregulated in lung cancer; however, its effect and mechanism on 5-fluorouracil (5-FU) resistance remain unclear. In this study, we determined the effects of FOXD3-AS1-enriched exosomes derived from lung cancer cells on the proliferation, invasion, and 5-FU resistance of lung cancer cells. Online bioinformatics database analysis showed that FOXD3-AS1 was upregulated in lung cancer progression. Real-time quantitative PCR results confirmed that FOXD3-AS1 expression was upregulated in lung cancer tissues and cell lines, and FOXD3-AS1 was greatly enriched in lung cancer cell-derived exosomes. ELAV-like RNA-binding protein 1 (ELAVL1) was identified as an RNA-binding protein of FOXD3-AS1. The lung cancer cell-derived exosomes promoted A549 cell proliferation and invasion and inhibited apoptosis caused by 5-FU, and transfection of si-FOXD3-AS1 or si-ELAVL1 in exosome-incubated A549 cells reversed these effects. Moreover, exosome-incubated A549 cells were co-transfected with si-FOXD3-AS1 and pcDNA-ELAVL1, showing the same cell proliferation, invasion, and 5-FU resistance as those of A549 cells treated with lung cancer cell-derived exosomes alone. Mechanistic studies identified that lung cancer cell-derived exosomes activated the PI3K/Akt pathway, and transfection of si-FOXD3-AS1 or treatment with the PI3K inhibitor LY294002 reversed the activation of the PI3K/Akt axis induced by exosomes. In conclusion, our study revealed that lung cancer cell-derived exosomal FOXD3-AS1 upregulated ELAVL1 expression and activated the PI3K/Akt pathway to promote lung cancer progression. Our findings provide a new strategy for lung cancer treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|