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Updated: Jul 16, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
miR-92a-3p regulates cisplatin-induced cancer cell death
Romain Larrue1, Sandy Fellah1, Nihad Boukrout1
1University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, 59000, Lille, France.
Abstract:
Non-small cell lung cancer is characterized by a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Therefore, the identification of new molecular determinants underlying sensitivity of cancer cells to existing therapy is of particular importance to develop new effective combinatorial treatment strategy. MicroRNAs (miRNAs), a class of small non-coding RNAs, have been established as master regulators of a variety of cellular processes that play a key role in tumor initiation, progression and metastasis. This, along with their widespread deregulation in many distinct cancers, has triggered enthusiasm for miRNAs as novel therapeutic targets for cancer management, in particular in patients with refractory cancers such as those harboring KRAS mutations. In this study, we performed a loss-of-function screening approach to identify miRNAs whose silencing promotes sensitivity of lung adenocarcinoma (LUAD) cells to cisplatin. Our results showed in particular that antisense oligonucleotides directed against miR-92a-3p, a member of the oncogenic miR-17 ~ 92 cluster, caused the greatest increase in the sensitivity of KRAS-mutated LUAD cells to cisplatin. In addition, we demonstrated that this miRNA finely regulates the apoptotic threshold and the proliferative capacity of various tumor cell lines with distinct genetic alterations. Collectively, these data suggest that targeting miR-92a-3p may serve as an effective strategy to overcome treatment resistance of solid tumors.
Insights
Targeting miR-92a-3p enhances cisplatin sensitivity in KRAS-mutated lung adenocarcinoma. Silencing this microRNA increases cancer cell sensitivity to chemotherapy, offering a new strategy for refractory tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) has poor outcomes due to late diagnosis and drug resistance.
- MicroRNAs (miRNAs) are key regulators of cellular processes and are often deregulated in cancer, making them potential therapeutic targets.
- KRAS-mutated lung adenocarcinomas (LUAD) are particularly challenging to treat due to resistance to standard therapies.
Purpose of the Study:
- To identify microRNAs that, when silenced, increase the sensitivity of lung adenocarcinoma cells to cisplatin.
- To investigate the role of specific microRNAs in regulating cancer cell apoptosis and proliferation.
- To explore novel therapeutic strategies for overcoming treatment resistance in solid tumors.
Main Methods:
- Conducted a loss-of-function screening approach to identify key microRNAs.
- Utilized antisense oligonucleotides to silence miR-92a-3p in KRAS-mutated LUAD cells.
- Assessed the impact of miRNA silencing on cisplatin sensitivity, apoptosis, and proliferation in various tumor cell lines.
Main Results:
- Silencing of miR-92a-3p, a member of the miR-17~92 cluster, significantly increased cisplatin sensitivity in KRAS-mutated LUAD cells.
- miR-92a-3p was found to regulate the apoptotic threshold and proliferative capacity of tumor cells.
- The study identified miR-92a-3p as a crucial regulator influencing chemosensitivity across different cancer cell lines.
Conclusions:
- Targeting miR-92a-3p represents a promising strategy to overcome cisplatin resistance in KRAS-mutated lung adenocarcinoma.
- Modulating miR-92a-3p levels can enhance the efficacy of chemotherapy in various solid tumors.
- This research provides a foundation for developing novel combinatorial treatments for refractory cancers.
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