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. 2019 Aug;8(9):4159-4168.
doi: 10.1002/cam4.2338. Epub 2019 Jun 13.

Circular RNA screening from EIF3a in lung cancer

Ma-Sha Huang  1   2 , Fu-Qiang Yuan  1   2 , Yang Gao  1   2 , Jun-Yan Liu  1   2 , Yi-Xin Chen  1   2 , Chen-Jing Wang  1   2 , Bai-Mei He  1   2 , Hong-Hao Zhou  1   2   3 , Zhao-Qian Liu  1   2   3
Affiliations

Circular RNA screening from EIF3a in lung cancer

Ma-Sha Huang et al. Cancer Med. 2019 Aug.

Abstract

Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs' biological functions is not well understood yet. In this work, we screened 31 EIF3a-derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA-binding proteins-mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer.

Keywords: EIF3a; bioinformatics; circular RNA; lung cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Panel A, EIF3a in different tissues, the data are obtained from THE HUMAN PROTEIN ATLAS (THPA) Database. Panel B, EIF3a in different cancers, the data are obtained from THE CANCER GENOME ATLAS (TCGA) Database. Panel C, The expression of EIF3a in various tumors, the data comes from ONCOMINE Database. EIF3a, eukaryotic translation initiation factor 3 subunit A
Figure 2
Figure 2
Panel A, The prognostic value of EIF3a level in lung cancer patients. Panel B, The prognostic value of EIF3a level in ovarian cancer patients. Panel C, Thirty‐one circRNAs derived from EIF3a. Panel D, The type and quantity of circEIF3as. EIF3a, eukaryotic translation initiation factor 3 subunit A. circRNA, circular RNA
Figure 3
Figure 3
Panel A, The expression of hsa_circ_0004350 and hsa_circ_0092857 in A549 and A549/DDP cell line. (*P < 0.05; **P < 0.01). The diagram of position: hsa_circ_0004350 (panel B) and hsa_circ_0092857 (panel C). Panel D, The half‐maximal inhibitory concentration of hsa_circ_0004350 and hsa_circ_0092857
Figure 4
Figure 4
Panel A, After RNase R treatment, the expression levels of EIF3a and circEIF3as were determined by qRT‐PCR. Panel B, Subcellular fractionation assay was used to detect the localization of hsa_circ_0004350 and hsa_circ_0092857. Panel C, RIP assay indicating that hsa_circ_0004350 and hsa_circ_0092857 were not substantially accumulated in the AGO2 pellet. Hsa_circ_0004350 and hsa_circ_0092857 has little effect on the expression of EIF3a according to qRT‐PCR (panel D) and western blot (panel E) assays. Panel F, Protein‐encoding potential of circEIF3as. EIF3a, eukaryotic translation initiation factor 3 subunit A. EIF3a, eukaryotic translation initiation factor 3 subunit A; qRT‐PCR, quantitative reverse transcription‐PCR; RIP, RNA immunoprecipitation assay
Figure 5
Figure 5
Panel A, The network of circEIF3as/RBPs axis. GO enrichment analysis of hsa_circ_0004350 (panel B) and hsa_circ_0092857 (panel C). Panel D, GO analysis on RBPs regulated by two circEIF3as. GO, gene ontology; RBPs, RNA‐binding proteins
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