MicroRNA Dysregulation in EGFR Exon 19 Deletion Lung Cancer
This month’s study focuses on microRNA dysregulation in EGFR Exon 19 Deletion, and its role in lung cancer, using the Human OneArray® MicroRNA, conducted at the Phalanx Biotech Lab. We feature an article from Lixia Ju and others of Tongji University Medical School Cancer Institute in Shanghai, China. The article was published 11 May 2017 in the Journal of Cancer and includes miRNA expression data generated by Phalanx Biotech’s service lab on our own Human miRNA OneArray® Microarray platform.
In the era of precision medicine, patient survival can increase by designing therapies specific to cancer subtypes. Lung cancer is a great example, as different somatic mutations in the EGFR gene are connected to differential sensitivity to the leading class of drugs. The authors seek to understand how the deletion of EGFR exon 19 affects the expression of miRNAs.
Using Human miRNA OneArray® Microarrays, the authors compare miRNA expression in EGFR exon 19 deletion cell lines (H1650 and PC9), and in EGFR wildtype cell lines (A549 and H1299). They find 8 miRNAs up-regulated, and 3 miRNAs down-regulated, in the EGFR exon 19 deletion lines. They further validate these miRNA targets with qPCR, and confirm up-regulation of hsa-miR-141-3p, hsa-miR-200c-3p, and hsa-miR-203, and down-regulation of hsa-miR-3196.
dPCR Validation and miRNA-Induced Drug Sensitivity
Interestingly, the authors note that both hsa-miR-200c-3p and hsa-miR-203 are known to affect EGFR and be associated with EGFR tyrosine kinase inhibitor (TKI) resistance. Next, the authors use Digital PCR (dPCR) to quantify hsa-miR-200c-3p, hsa-miR-203, and hsa-miR-3196 in 27 human patients, composing an EGFR wildtype group and an EGFR exon 19 deletion group. They choose dPCR because they recognize that cancer-related miRNAs are likely rare targets within a larger background of wildtype miRNAs. This is indeed true for tumor samples and liquid biopsy samples. Within these contexts, dPCR offers better sensitivity than traditional qPCR. The dPCR results reveal that hsa-mir-3196 is down-regulated in patients with EGFR exon 19 deletion. This result is consistent with the microarray and qPCR results.
The authors next focus on whether hsa-mir-3196 expression has an effect on sensitivity to erlotinib, an EGFR TKI approved for the treatment of lung cancer. They show that induced up-regulation of hsa-mir-3196 in EGFR Exon 19 deletion/erlotinib-treated cells caused a slight decrease in apoptosis relative to control samples. They also show that inhibition of hsa-mir-3196 in EGFR wildtype/erlotinib-treated cells caused a slight increase in apoptosis relative to control samples. These results further point to an interconnected network involving EGFR exon 19 deletion, down-regulation of hsa-mir-3196, and sensitivity to EGFR TKIs.
In summary, this study shows that miRNA profiling is a powerful technique for elucidating the cellular networks present following rare somatic mutations that give rise to precise cancer subtypes. The authors point to the need for follow-up studies to completely understand how EGFR exon 19 deletion and hsa-mir-3196 are related, and how they modulate sensitivity to EGFR TKIs. Once the pathways are completely understood, hsa-mir-3196 might represent a very appealing candidate for targeted lung cancer therapy.
At Phalanx Biotech, we are your partners in driving discovery. Please contact us if you’re interested in our miRNA expression profiling services, similar to what was conducted in the paper described in this Research Highlight. We offer gene expression profiling services on both Agilent and our own OneArray platforms. We also can perform qPCR services for both microarray validation purposes or for more targeted approaches to gene expression profiling. Please visit our qPCR Services webpage for more information.
Ju L et al. MicroRNA Signature of Lung Adenocarcinoma with EGFR Exon 19 Deletion (2017). Journal of Cancer 8(7): 1311-1318.