Abstract
Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth in vivo. We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.
Highlights
Lung carcinoma carries the highest incidence and mortality among cancers [1]; we divide it into small cell and non-small cell lung cancer (NSCLC)
We considered DE-mRNAs, DE-miRNAs, and DE-Long non-coding RNAs (lncRNAs) with the same expression trend intersecting from 100 μM ivosidenib group of A549 and SK-MES-1 as common DE-mRNAs, DEmiRNAs, and DE-lncRNAs compared to control
To further understand the potential function of mRNAs and to provide useful information for experiments, we identified a lncRNA-miRNA-mRNA axis based on the results of the functional analysis
Summary
Lung carcinoma carries the highest incidence and mortality among cancers [1]; we divide it into small cell and non-small cell lung cancer (NSCLC). In a large population study, a total of 298 lung carcinoma samples [179 samples by Kang et al [9], 107 samples by Bleeker et al [10], and 12 samples by Tan et al [11]] showed no IDH1 mutations. Rodriguez et al analyzed IDH1/2 mutations in 1924 NSCLC specimens (92% adenocarcinoma) using next-generation sequencing and identified IDH1/2 mutations in nine (0.5%) adenocarcinomas [12] These findings suggest that mIDH1 in NSCLC is relatively rare. A study showed that knockdown of IDH1 by RNA interference reduced the proliferative capacity of NSCLC cells and significantly decreased in vivo xenograft tumor formation, suggesting that IDH1 may be a potential target in lung cancer [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
