This month’s featured article is from the lab of Longbang Chen of Nanjing University School of Medicine in Nanjing, China. The article was published 31 Mar 2017 in the journal Oncology Letters.
This study focused on drug-resistant small cell lung cancer (SCLC), and more specifically, the molecular mechanisms underlying the development of drug resistance. Treatment with etoposide (V16) and cisplatin (DPP) is a common first-pass chemotherapy treatment of SCLC, however, patients often develop resistance to the chemotherapy, thus leading to relapse and/or progression of SCLC. The authors sought to compare gene and miRNA expression in naïve vs. drug-resistant SCLC cell lines. They reasoned that differentially expressed genes and miRNAs would point to the mechanism of drug resistance and thereby identify novel therapeutic targets for the prevention of drug resistance.
The authors generated their drug resistant cell line by continuous exposure of an SCLC cell line to V16 and DPP. They ramped up the concentrations of V16 and DPP over 10 months. The treated cells were morphologically distinct from the parental cells, and most importantly, showed the following hallmarks of drug resistance: 1) they were more resistant to V16/DPP than their parental cells; 2) they were also resistant to other anticancer drugs, and 3) the expression level of P-glycoprotein was increased compared to their parent cells.
To compare the gene and miRNA expression profiles of control and resistant SCLC cells, the authors used Phalanx Biotech’s Human OneArray Whole Genome Microarray and Human miRNA OneArray Microarray. The whole genome microarray pointed to 75 up-regulated and 40 down-regulated genes. The authors then validated the expression of 42 of these genes using qPCR and found the microarray and qPCR results to be 95% consistent. The miRNA microarray pointed to 15 up-regulated and 16 down-regulated miRNAs. In the heatmap shown above, the 31 differentially expressed miRNAs show very clearly that miRNA expression is somehow involved in the development and/or maintenance of drug resistance. The authors went a step further with the differential gene expression data showing the many biological processes enriched in the list of genes, including the p53 hypoxia pathway, apoptosis, the transforming growth factor β signaling pathway, colorectal cancer, basal cell carcinoma, and the Wnt signaling pathway.
In summary, the authors developed a drug-resistant SCLC cell line that can be utilized to further study the mechanisms of drug resistance. They also identified numerous gene and miRNA targets underlying the development/maintenance of drug resistance. Further studies focusing on the exact mechanisms of drug resistance in SCLC hold great potential in identifying therapeutic targets.
At Phalanx Biotech, we are your partners in driving discovery. Please contact us if you’re interested in gene expression profiling or miRNA expression profiling, similar to what was conducted in this month’s Research Highlight. If performing both gene expression and miRNA expression profiling, our bioinformatics team has developed an integrated analysis that maps putative targets of differentially expressed miRNAs and then looks for those targets in your list of differentially expressed genes. The result is a functional genomics interpretation of the microarray data, which will help you move from individual genes to higher level pathways and biological processes.
Chen Y et al. Genomic analysis of drug-resistant small cell lung cancer cell lines by combining mRNA and miRNA expression profiling (2017). Oncology Letters 13: 4077-4084.