Abstract
Lung cancer constitutes 85% of non-small cell lung cancer diagnosed cases. MicroRNAs are novel biomarkers that are capable of modulating multiple oncogenic pathways. Epigallocatechin-3-gallate (EGCG) is a potent chemopreventive and chemotherapeutic agent for cancer. We aimed to identify important known and putative novel microRNAs modulated by EGCG in A549 cells using next-generation sequencing and identify their gene targets. Preliminary analysis revealed an IC50 value of 309 μM with G0/G1 phase arrest at 40 μM EGCG treatment. MicroRNA profiling identified 115 known and 4 putative novel microRNAs in 40 μM and 134 known and 3 putative novel microRNAs in 100 μM EGCG-treated A549 cells. The top 10 up-expressed microRNAs were similar between the untreated control and EGCG-treated A549 cells. An up-expression in oncogenic microRNAs, which belong to broadly conserved seed families, were observed in untreated control and EGCG-treated A549 cells. Kyoto Encyclopedia of Genes and Genomes and Protein Analysis Through Evolutionary Relationships pathway analyses of the validated microRNA targeting genes strengthened the hypothesis that EGCG treatment can modulate microRNAs that play a significant role in the MAPK signaling pathway. Expression profile of microRNAs was validation by quantitative real time PCR of randomly selected microRNAs. This study identified signature microRNAs that can be used as novel biomarkers for lung cancer diagnosis.
Highlights
Green tea, brewed from the unfermented dry leaves of the plant Camellia sinensis, is the most consumed non-alcoholic beverage in Asian countries and is gaining popularity in western countries as well
The oncogenic microRNAs were highly up-expressed in the untreated control and EGCG-treated
Our data indicated EGCG as an effective natural compound which regulates microRNA profile in A549 cells
Summary
Green tea, brewed from the unfermented dry leaves of the plant Camellia sinensis, is the most consumed non-alcoholic beverage in Asian countries and is gaining popularity in western countries as well. It contains a wide range of phytochemicals which exhibits anti-cancer, anti-oxidative, and anti-inflammatory properties [1]. Among these phytochemicals, (−)-epigallocatechin-3-gallate (EGCG) accounts for 18–36% of the total phenolic compounds and 70% of the catechins present in green tea. EGCG is a potential chemopreventive and chemotherapeutic compound against skin [2], lung [3], breast [4], colon [5], prostate [6], and other cancers [7,8].
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