Related Experiment Video
Updated: May 24, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
miR-34c may protect lung cancer cells from paclitaxel-induced apoptosis
S Catuogno1, L Cerchia, G Romano
1Istituto per l'Endocrinologia e l'Oncologia Sperimentale del CNR 'G Salvatore', Naples, Italy.
Abstract:
MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively regulate the expression of their target genes. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and are considered as promising new therapeutic targets for cancer. However, the identity of miRNAs involved in apoptosis and their respective targets remain largely unknown. Given the elevated complexity of miRNA regulation of gene expression, we performed a functional screening as an alternative strategy to identify those miRNAs that in lung cancer cells may interfere with the apoptotic process. To this aim, we generated a derivative of the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical upstream initiator of apoptosis, can be activated by administration of the small dimerizer drug AP20187. We found a number of miRNAs that may rescue cell viability from caspase-8 activation. They included miRNAs already described as oncogenic such as miR-17, miR-135 and miR-520, but also some miRNAs such as miR-124-1 and miR-34c for which a tumor-suppressive role has instead been described or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel-induced apoptosis. We demonstrate that Bmf (Bcl-2-modifying factor) is a target of miR-34c-5p, and that its silencing, together with that of c-myc, a known target of miR-34c-5p, contributes to resistance to apoptosis induced by paclitaxel through p53 downregulation.
Insights
This study identifies microRNAs (miRNAs) that influence apoptosis in lung cancer cells. miR-34c-5p was found to confer resistance to paclitaxel-induced apoptosis by targeting Bmf and c-myc, impacting p53 signaling.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression and are implicated in cancer.
- Identifying miRNAs involved in apoptosis and their targets is crucial for cancer therapy.
- The precise role of many miRNAs in cancer-related apoptosis remains largely unknown.
Purpose of the Study:
- To functionally screen and identify microRNAs that interfere with apoptosis in lung cancer cells.
- To investigate the role of specific miRNAs, such as miR-34c-5p, in resistance to apoptosis.
- To elucidate the molecular mechanisms by which identified miRNAs affect apoptosis.
Main Methods:
- Functional screening of microRNAs in a modified A549 non-small cell lung carcinoma cell line.
- Activation of caspase-8, a key apoptosis initiator, using the dimerizer drug AP20187.
- Validation of miRNA targets (Bmf, c-myc) and assessment of their impact on apoptosis and p53 signaling.
Main Results:
- Several miRNAs were identified that rescue cell viability upon caspase-8 activation, including oncogenic (miR-17, miR-135, miR-520) and tumor-suppressive (miR-124-1, miR-34c) miRNAs.
- miR-34c-5p significantly enhanced resistance to paclitaxel-induced apoptosis.
- Bmf and c-myc were confirmed as targets of miR-34c-5p, and their downregulation contributed to paclitaxel resistance via p53 downregulation.
Conclusions:
- Functional screening is a viable strategy to identify apoptosis-modulating miRNAs in lung cancer.
- miR-34c-5p acts as an oncomiR in this context, promoting resistance to chemotherapy-induced apoptosis.
- Targeting miR-34c-5p or its downstream effectors (Bmf, c-myc) may offer novel therapeutic strategies for lung cancer.
Related Concept Videos
01:15Drugs that Stabilize Microtubules
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...