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Additional file 1: Supplementary Figure 1. Expression levelsof different circRNA in patients.Expression levels of Circ_0001187 in AML cell lines. The expressions of Circ_0011929 and Circ_0000973 in AML patients and healthy controls.Relative expression of Circ_0001187 in gender was measured by qRT-PCR.Expression levels of Circ_0001187 and linear DOPEY2 mRNA in THP-1 cellsafter being treated with RNase R by qRT-PCR. Data were analyzed using Unpairedt-test.Expression levels of Circ_0001187 and linearDOPEY2 mRNA in Molm-13 AML cells treated with actinomycin D by qRT-PCR. The qRT-PCR expression results of Circ_0001187 and DOPEY2 using randomprimer and Oligo dT primer in Molm-13 AML cells. The qRT-PCR analysis of nuclear and cytoplasmic fractionation extractsin THP-1 andMolm-13 AML cells. The results of RNA FISH by using sense probein THP-1 and Molm-13 AML cells. **p < 0.01; ****p < 0.0001;ns: Not significant. Supplementary Figure 2. The qRT-PCR results of Circ_0001187 in THP-1 and Molm-13 cells withCirc_0001187 knockdown or overexpression. The proliferation results of THP-1 cellstransfected si-Circ1 or si-Circ 2 by EDU staining. The expression levelof differential genes by RNA-seq analysis.KEGG pathways in Circ_0001187 knockdown compared to the control group.GSEA analysis for Circ_0001187 knockdown compared to the controlgroup. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Supplementary Figure 3. The qRT-PCR results of Circ_0001187 in mice treatedwith sh-Circ compared with negative control. The spleen weight of AML mice injectedwith THP-1 cells transfected with sh-Circ_0001187-GFP or Ctrl-GFP.Differential expression of miRNA from RNA pull-down.miRNA and target mRNA predictionnetwork of Circ_0001187 via RNA pulldown assay. The results of GO enrichment correspond tomiRNA/mRNA. *p < 0.05; ***p < 0.001. Supplementary Figure 4. The results of coomassie blue staining inTHP-1with Circ_0001187 knockdown. The protein METTL3 identified by mass spectrometryanalysis. The qRT-PCR results of METTL3 in THP-1 and Molm-13 AML cells with Circ_0001187 knockdown.Western blot results of METTL3 in 293-T cells treated with 20 μg/ml CHX at different times. The mRNA leve of MYB, MYC and ITGA4 in THP-1and Molm-13AML cells with Circ_0001187 knockdown. The potential METTL3 E3 ligases identifiedby affinity MS.Western blot results of METTL3in THP-1 cells transduced with the siRNA of potentialE3 ligases respectively compared with negative control. The expression levels of RNF113A from TCGA database. The proliferation results of THP-1 and Molm-13cells with RNF113A knockdown by CCK-8 assays. The effect of RNF113A knockdown on theapoptosis of THP-1 and Molm-13 cells by flow cytometry. *p < 0.05; **p< 0.01; ***p < 0.001; ****p < 0.0001; ns: Not significant. Supplementary Figure 5. The results of RNA FISH by using sense probe in THP-1 and Molm-13 AML cells. The effect of miR-499a-5p mimics on theproliferation of THP-1 and Molm-13 cells. The effect of miR-499a-5p mimics onthe apoptosis of THP-1 and Molm-13 cells.ChIP‒qPCR showingthe effect of chidamide on the histoneacetylation levels of Circ_0001187 by promoters in THP-1 and Molm-13 cells. TheRNA-bing protein sites matching flanking regions of circRNA from Circintercomedatabase. The results from RBPsuit database. The expression levels of EIF4A3 from TCGAdatabase. The effect of oe-EIF4A3or oe-EIF4A3/siCirc on the proliferation of THP-1 cells. The effect of oe-EIF4A3 or oe-EIF4A3/siCircon the apoptosis of THP-1 cells. *p < 0.05; **p

Additional file 1: Fig. S1. The correlation of CDH23 and blasts percentage. A The different proportion of blast cells between high and low CDH23 mRNA level in TCGA cohort (P=0.291). B The spearman correlation analysis between the CDH23 expression level and blast percentage in TCGA cohort (Spearman’s correlation: -0.078, P=0.35).

BackgroundAcute myeloid leukemia (AML) is a fatal hematopoietic malignancy which has a prognosis that varies with genetic heterogeneity of its hematopoietic stem/progenitor cells(HSCPs). Intensive induction chemotherapy with cytarabine and anthracycline has been the standard of care for newly diagnosed AML, but about 30% of patients have no response to this regimen. The resistance mechanisms require deeper understanding. Methods In our study, using 10× Genomics, a high-throughput single cell RNA sequencing (scRNA-seq) platform, we analyzed the cellular heterogeneity of bone marrow CD34+ cells from newly diagnosed AML patients who were then divided into sensitive and resistant groups according to their responses to induction chemotherapy with cytarabine and anthracycline. ScRNA-seq data for healthy controls were obtained from the GEO database. We verified our findings by the TCGA database, GEO datasets and the multiparameter flow cytometry.ResultsFrom the integrative analysis of 60,402 cells, we established a landscape for single-cell CD34+ cells in AML patients and identified the hematopoietic stem/progenitor cell types based on the lineage signature genes. Interestingly, through recognizing the malignant-like clusters and comparing “resistant group” with “sensitive group”, we found a cell population with specific gene signatures (CRIP1highLGALS1highS100Ashigh) showing features of granulocyte-monocyte progenitors (GMP) was associated with poor prognosis of AML. And two cell populations of AML CD34+ cells marked by CD52+ or CD74+DAP12+ were related to good response of patients to induction therapy, showing characteristics of hematopoietic stem cell (HSC). ConclusionOur study indicates the heterogeneity of AML CD34+ cells confers for outcomes of AML and provides possible biomarkers to predict the response of AML patients to induction chemotherapy.

Jun Jiao,1 Xinlin Jiao,1 Qingqing Liu,1 Wenjie Qu,1 Daoxin Ma,2 Youzhong Zhang,1 Baoxia Cui1 1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Hematology Oncology Center, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of ChinaCorrespondence: Baoxia Cui Tel +8618560081862Email cuibaoxia@sdu.edu.cnPurpose: Accumulating evidence indicates that circular RNAs (circRNAs) are closely involved in canceration and cancer progression. However, the role of circRNAs in cervical cancer (CC) is largely unknown. Here, we characterized the role of circRNA_101308 in CC.Materials and Methods: The expression of circRNA_101308 in CC tissues was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, circRNA_101308 was overexpressed in CC cells to detect its function by proliferation and apoptosis assays, Transwell assays and animal experiments. The potential mechanism of circRNA_101308 in CC was explored by RNA pull-down, Gene Ontology (GO) and pathway analyses.Results: CircRNA_101308 was significantly downregulated in CC tissues. The level of circRNA_101308 was much lower in CC patients with lymph node metastasis or deep myometrial invasion compared to those patients without lymph node metastasis and superficial myometrial invasion. CircRNA_101308 overexpression inhibited CC cell proliferation, invasion and migration. MiR-26a-5p, miR-196a-5p, miR-196b-5p, miR-335-3p, and miR-1307-3p were found to be sponged by circRNA_101308 in CC cells. Further, GO and pathway analyses predicted the potential functional processes and pathways of circRNA_101308 in CC.Conclusion: CircRNA_101308 is downregulated and acts as a tumor suppressor in CC. CircRNA_101308 can participate in many different processes by sponging different miRNAs in CC cells. This exploration of circRNA_101308 provides new directions for research on cancer development and the clinical treatment of CC.Keywords: circular RNA, cervical cancer, circRNA_101308, microRNA