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MicroRNA-25-3p promotes cisplatin resistance in Non-small-cell lung carcinoma (NSCLC) through adjusting PTEN/PI3K/AKT
Butong Sun1, Nanjun Hu1, Dan Cong1
1Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun City, China.
Abstract:
MicroRNAs exert crucial effects in the drug resistance. The purpose of this research was to investigate the miR-25-3p effects on DDP resistance in NSCLC. We used RT-qPCR to evaluate the expression of miR-25-3p. Cell growth was determined using MTS assay. Cellular bio-activity was analyzed via Colony formation, Annexin V/PI, and Transwell assay. Luciferase reporter assay was used to determine miR-25-3p and PTEN binding. Western blot was used to determine PTEN, PI3K, p-AKT/AKT expression. In-vivo study was used to determine the effects of miR-25-3p on the tumor growth. Expression of miR-25-3p is increased in NSCLC cisplatin resistant A549 and H1299 cells. Furthermore, miR-25-3p mimic enhanced drug resistance, and accelerated cell invasion and metastasis. Moreover, miR-25-3p mimic resulted in the activation of PTEN/PI3K/AKT pathway. However, miR-25-3p inhibitors exhibited the opposite trend. We further identified PTEN as a potential target of miR-25-3p. PTEN knockout promoted cisplatin resistance, while PTEN mimic displayed opposite effects. Interestingly, miR-25-3p further boosted cisplatin resistance cells in vivo, and miR-25-3p inhibitors reduced the in-vivo tumor volume. MiR-25-3p/PTEN/PI3K/AKT axis might accelerate DDP tolerance in NSCLC, which may serve as a potential target for chemotherapy resistance in NSCLC.
Insights
MicroRNA miR-25-3p increases cisplatin resistance in non-small cell lung cancer (NSCLC). Targeting this microRNA and the PTEN/PI3K/AKT pathway may overcome chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Drug resistance is a major challenge in non-small cell lung cancer (NSCLC) treatment.
- MicroRNAs play significant roles in regulating cellular processes, including drug resistance.
Purpose of the Study:
- To investigate the role of miR-25-3p in cisplatin (DDP) resistance in NSCLC.
- To elucidate the underlying molecular mechanisms, including the PTEN/PI3K/AKT pathway.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) for miR-25-3p expression.
- Cell viability (MTS assay), colony formation, apoptosis (Annexin V/PI), and invasion (Transwell) assays.
- Luciferase reporter, Western blot, and in vivo tumor growth studies.
Main Results:
- miR-25-3p expression was elevated in cisplatin-resistant NSCLC cells.
- miR-25-3p mimic enhanced DDP resistance, invasion, and metastasis, activating the PTEN/PI3K/AKT pathway.
- PTEN was identified as a direct target of miR-25-3p; PTEN inhibition mimicked miR-25-3p effects.
- In vivo studies confirmed miR-25-3p promotes tumor growth and DDP resistance.
Conclusions:
- The miR-25-3p/PTEN/PI3K/AKT axis promotes cisplatin resistance in NSCLC.
- This axis represents a potential therapeutic target for overcoming chemotherapy resistance in NSCLC.
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