MiR-30a sensitized lung cancer against neoadjuvant chemotherapy by depressing autophagy
Xiao Lin, Xiaojing Lai, Wei Feng
1Department of Thoracic Radiotherapy, The Cancer Hospital of the University of Chinese Academy of Science (Zhejiang Cancer Hospital), Hangzhou City, China.
Objective:
This study was aimed at exploring whether miR-30a enhanced sensitivity of non-small-cell lung cancer (NSCLC) cells against neoadjuvant chemotherapy through an autophagy-dependent way.
Methods:
We totally recruited 304 NSCLC patients who have underwent chemotherapy, as well as 185 NSCLC patients who did not receive chemotherapy. NSCLC cell lines (i.e. H1299 and H460) were also purchased, and they were transfected by miR-30a mimic/inhibitor. Furthermore, cisplatin (DDP)/pemetrexed (PEM) resistance of NSCLC cells was assessed utilizing MTT assay, and autophagic proteins isolated from NSCLC tissues and cells were quantitated by western blotting.
Results:
Lowly expressed miR-30a was reflective of lymph node metastasis, advanced TNM stage and poor 5-year survival among NSCLC patients treated by neoadjuvant chemotherapy (i.e. combined treatment of DDP and PEM) (P < 0.05). Moreover, DDP combined with PEM attenuated viability and proliferation, but, on the contrary, promoted autophagy of H1299 and H460 cell lines (P < 0.05). However, miR-30a undermined resistance of NSCLC cells against DDP and PEM (P < 0.05), and it suppressed DDP/PEM-induced autophagy and promoted DDP/PEM-triggered apoptosis of NSCLC cells (P < 0.05).
Conclusions:
Intentionally elevating miR-30a expression was conducive to improving NSCLC prognosis after neoadjuvant chemotherapy, for its depressing drug-caused autophagy and resistance.
Insights
Elevating miR-30a expression improves non-small-cell lung cancer (NSCLC) outcomes after neoadjuvant chemotherapy. This microRNA reduces drug resistance and autophagy, enhancing treatment effectiveness and patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- Neoadjuvant chemotherapy is a standard treatment for advanced NSCLC, but drug resistance poses a significant challenge.
- Autophagy, a cellular self-degradation process, plays a complex role in cancer progression and treatment response.
Purpose of the Study:
- To investigate the role of miR-30a in modulating the sensitivity of NSCLC cells to neoadjuvant chemotherapy.
- To determine whether miR-30a influences chemotherapy response through an autophagy-dependent mechanism.
Main Methods:
- Analysis of miR-30a expression in 304 NSCLC patients treated with neoadjuvant chemotherapy versus 185 untreated patients.
- In vitro studies using NSCLC cell lines (H1299, H460) transfected with miR-30a mimics or inhibitors.
- Assessment of cell viability, proliferation, and apoptosis using MTT assays and western blotting for autophagic proteins.
Main Results:
- Low miR-30a expression correlated with lymph node metastasis, advanced TNM stage, and poorer 5-year survival in NSCLC patients receiving neoadjuvant chemotherapy.
- Chemotherapy drugs (cisplatin/pemetrexed) attenuated NSCLC cell viability but induced autophagy.
- Overexpression of miR-30a reduced NSCLC cell resistance to chemotherapy, suppressed chemotherapy-induced autophagy, and promoted chemotherapy-triggered apoptosis.
Conclusions:
- Elevating miR-30a expression is a promising strategy to enhance NSCLC patient prognosis following neoadjuvant chemotherapy.
- miR-30a functions by suppressing chemotherapy-induced autophagy and overcoming drug resistance in NSCLC.
- Targeting miR-30a may represent a novel therapeutic approach to improve outcomes in NSCLC patients.
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