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Cancer is a major public health problem worldwide. Studies on oncogenes and tumor-targeted therapies have become an important part of cancer treatment development. In this review, we summarize and systematically introduce the gene enhancer of rudimentary homolog (ERH), which encodes a highly conserved small molecule protein. ERH mainly exists as a protein partner in human cells. It is involved in pyrimidine metabolism and protein complexes, acts as a transcriptional repressor, and participates in cell cycle regulation. Moreover, it is involved in DNA damage repair, mRNA splicing, the process of microRNA hairpins as well as erythroid differentiation. There are many related studies on the role of ERH in cancer cells; however, there are none on tumor-targeted therapeutic drugs or related therapies based on the expression of ERH. This study will provide possible directions for oncologists to further their research studies in this field.

Additional file 3: Table S3. The list of predicted miRNAs.

Additional file 8: Table S3. The percentages of non-apoptotic cells in the different phases of the cell cycle. The data were calculated based on the results in the histograms indicating a representative cell cycle (Fig. 6).

Additional file 1: Supplementary Figure 1. (A) Sample clustering and (B) the analysis of the scale-free index for various soft-thresholding powers (��). (C) Scatterplot show the correlations between gene module membership in the blue module and gene significance for sorafenib response. (D) Overall survival analysis of the top-10 enhanced miRNAs in the blue module. Data was retrieved from Kaplan-Meier Plotter of liver cancer with default setting. (E) MiR-23a-3p expression between HCC and NAT. Unpair t-test, P > 0.05. (F) MiR-23a-3p expression among different grades of HCC. One-way ANOVA, P > 0.05. (G) Univariable analysis of the association between survival and clinicopathologic factors. Supplementary Figure 2. (A) Body weight of mice was recorded every 3 days. The arrow indicates the start of sorafenib administration. WT: vehicle group; R1���5: sorafenib-treated group. (B) Body weight of re-injected mice (n = 5). WT: mice with parental cells; R1/3/5: mice with in vivo-generated sorafenib resistant cells. Supplementary Figure 3. (A) The IC50 value of sorafenib in MHCC97L and PLC/PRF/5 by MTT assay. (B) The expression of p-ERK was downregulated after different doses of sorafenib treatment, indicating the effective response to sorafenib (C) The inhibition of ETS1 siRNAs on ETS1 mRNA and protein expression. Three biological replicates were conducted independently in all experiments above. One-way ANOVA, *P

Additional file 5: Fig. S5. Upregulation of CDK6 in MDR KB-C2 cells compared to KB-3-1 cells. Transcriptome sequencing and quantification were performed in the MDR KB-C2 cells and drug sensitive parental KB-3-1 cells in the same condition, and the data showing the level of all the cdk6 transcripts is summarized in this graph. As indicated by the transcripts per million mapped reads (TPM) value, the number of full-length-cdk6 transcripts (mRNA) in KB-C2 cells were 7-folds of that in KB-3-1 cells. The transcripts ENST00000265734 and ENST00000424848 corresponding to the full-length of CDK6 protein were indicated by *.

Additional file 2: Table S2. Antibody information.

Additional file 1: Table S1. Primers and DNA/RNA srquence used in this study.

Additional file 1: Supplementary Word 1. h-RHOB 3-UTR reporter vector.

Additional file 3: Fig. S3. Regulation of CDK6 on ABCB1-mediated MDR in H460/MX80. A RT-PCR certification of cdk6 or cdk4 gene knockout in H460/MX80 cells. The cells were transfected with the CRISPR/Cas9 all-in-one plasmid and stabilized for 2 weeks and then analyzed for the cdk4 or cdk6 mRNA amounts. B MTT analysis of cell viability of MDR H460/MX80 cells (with very low level of ABCB1 expression) and the cdk6-deficient H460/MX80 cells, i.e., H460/MX80-k.o.cdk6 cells. Paclitaxel and colchicine, which are ABCB1 substates, were used for co-culture with H460/MX80 and H460/MX80-k.o.cdk6 cells for 72 h.

Additional file 6: Table S1. Differential expression of CDK6, ABCB1, CDK4, PIK3CA, PIK3CB and GAPDH genes in KB-C2 and KB-C2-k.o.cdk6. Identical amounts of total RNA from KB-C2 and KB-C2-k.o.cdk6 cells were analyzed for transcriptome sequences and differential gene expression. The transcripts encoding full or effective length of proteins are listed.

Additional file 1.

Additional file 2: Supplementary Table S1. Oligos used in the study.

Additional file 2: Fig. S2. Protein-protein interaction of the proteins which are most correlated with endocrine resistance.

Additional file 1: Fig. S1. Network and the interactions of the Top10 differentially expressed genes involved in KEGG Endocrine resistance. A Network of enriched terms colored by cluster ID, where nodes that share the same cluster ID are typically close to each other. B Protein-protein interaction network and components identified in the gene lists. String platform was used for the analysis.

Additional file 7: Table S2. Downregulation of the expression level of CDK6 in KB-C2-k.o.110α, KB-C2-k.o.110β, MX80-k.o.110α, or MX80-k.o.110β populations.

Additional file 1: Supplementary Figure 1. The expression and function of hsa_circ_0003258 in PCa. (A). The heatmap showing some of the differentially expressed circRNAs between normal and prostate cancer patient plasma samples. (B). The representative images of FISH analysis of hsa_circ_0003258 in normal and PCa tissues. (C). The protein coding potential of hsa_circ_0003258. (D). The melting curve of hsa_circ_0003258 amplified product using the divergent primers. (E-H). Transwell assay detecting the migratory capacity of PCa cells after transfecting with siRNAs or vector plasmid. (I-J). Colony formation assays and CCK8 assays were utilized to evaluate the proliferation of PCa cells after knockdown of hsa_circ_0003258 in DU145 and C4���2 cells. ns: Not Significant. Supplementary Figure 2. Hsa_circ_0003258/ miR-653-5p/Arhgap5 pathway in C4-2. (A). The heatmap of differentially expressed mRNAs in DU145/sh-nc and DU145/sh- hsa_circ_0003258 cells. Each sample was mixed in three replicates. (B). Transwell assay detecting the migratory capacity of PCa cells after SCH772984 treatment for 48 h in DU145 Lv- hsa_circ_0003258 cells. (C). The potential binding miRNAs predicted by CircInteractome database. (D). Lysates from C4���2 cells was subjected to biotinylated-hsa_circ_0003258 pull-down assay and the expression levels of hsa_circ_0003258 were measured by qRT-PCR. (E). The expression levels of the top three candidate miRNAs predicted by Circinteractome database quantified by qRT-PCR after biotinylated-hsa_circ_00032583 pull-down assay in C4���2 cells. (F). The relative expression of hsa_circ_0003258 detected by qRT-PCR after the transfection of miR-653-5p mimic or inhibitor. (G-H). The qRT-PCR and Western blot showing the ARHGAP5 mRNA and protein level change of the predicated targets after silencing or overexpression of hsa_circ_0003258. (I-J). The qRT-PCR and Western blot showing the ARHGAP5 mRNA and protein level change of the predicated targets after silencing or overexpression of miR-653-5p. ns: Not Significant; * P

Additional file 4: Fig. S4. Upregulation of ABCB1 in MDR KB-C2 cells compared to KB-3-1 cells. Transcriptome sequencing and quantification were performed in the MDR KB-C2 cells and drug sensitive parental KB-3-1 cells in the same condition, and the data showing the level of all the ABCB1 transcripts is summarized in the graph. As indicated by the transcripts per million mapped reads (TPM) value, the number of full-length-ABCB1 transcripts (mRNA) in KB-C2 cells were substantially increased as compared with that in KB-3-1 cells. The transcripts ENST00000265724, ENST00000622132 and MSTRG.27385.1 corresponding to the full-length of ABCB1 protein were indicated by *.

Additional file 1.

Additional file 3: Figure S3. The effect of Spautin-1 on the autophagy and cytotoxity caused by BKM120. Representative images of autophagosome puncta (A) in SKOV-3 and MKN-1 treated with BKM120 (1 ��M), Spautin-1 (10 ��M), alone or in combination for 24 h, and the quantification (B). Scale bars, 20 ��m. (C) Cell viability of HBC-5 cells after treated with different concentrations of BKM120 alone or in combination with 10 ��M Spautin-1 for 72 h. (D) Colony forming ability of HBC-5 cells after treated with Spautin-1 or/and BKM120. Graph of colony quantification is shown in (E). Graphs are normalized to 100% per treatment and shown as mean �� SD from three independent experiments; ns: p > 0.05; **p

Additional file 6: Figure S6. ROS inducers synergized with BKM120 to exhibit anti-proliferative effect in MKN-1 cells. (A) Determination of ROS production in MKN-1 cells treated with BKM120 and/or Cisplatin/Doxorubicin for 48 h. (B) Cell viability was measured by PrestoBlue after treatment with BKM120 alone or in combination with Cisplatin/Doxorubicin for 72 h. Graphs are normalized to the untreated group and shown as the mean �� SD from three independent experiments; *p

Additional file 4: Figure S4. Silence of Atg5 or Atg7 did not affect the anticancer activity of BKM120 and other PI3K inhibitors. (A) Western blot analysis of Atg5 and Atg7 in SKOV-3 and MKN-1 cells after transfection with non-targeting siRNA (siNT), Atg5 and Atg7 siRNA, respectively. (B) Cell viability of SKOV-3 and MKN-1 cells after transfected with Atg7 siRNA, followed by treatment of BKM120 for 72 h. (C) Colony forming ability of SKOV-3 and MKN-1 cells after transfected with non-target siRNA or Atg7 siRNA and treated with BKM120 for 72 h and allowed to recover in fresh media for 7���10 days. Graph of colony quantification is shown in (D). (E) Cell viability of MKN-1 cells after transfected with Atg5 or Atg7 siRNA, followed by treatment of BAY 80-6946 or GDC-0941 for 72 h. Graphs are normalized to 100% per treatment and shown as mean �� SD from three independent experiments; ns: p > 0.05.

Additional file 2: Figure S2. HCQ increased the sensitivity of the other PI3K inhibitors in MKN-1 cells. (A) Western blot analysis of LC3B and p62 in MKN-1 cells treated with BKM120 and/or HCQ for 48 h. (B) Cell viability was measured by PrestoBlue after treatment with BAY 80-6946/GDC-0941 alone or in combination with 20 ��M HCQ for 72 h. (C) Colony-forming abilities of cells treated with HCQ and/or BAY 80-6946/GDC-0941 were determined. Colony quantification is graphed in (D). (E) Western blot analysis of PI3K-p110��, p-Akt, Akt and p-mTOR after siRNA knockdown of PI3KCA. (F) The cells were treated with HCQ for 48 h in the presence or absence of PI3KCA siRNA, and cell apoptosis was measured. Graphs are normalized to 100% per treatment and shown as mean �� SD from three independent experiments; *p

Additional file 1: Figure S1. Inhibition of PI3K suppressed cell proliferation and induced apoptosis in tumor cells. (A) The three tumor cell lines were treated with different concentrations of BKM120 for 48 h. Cell viability was determined by PrestoBlue assay. (B) The cells were treated with indicated concentrations of BKM120 for 48 h and subjected to Annexin V-FITC/PI staining and flow cytometric analysis of apoptosis. (C) FACS quantification of total apoptotic cell population including Annexin V+/propidium iodide���early apoptotic cells and Annexin V+/propidium iodide+late apoptotic cells. (D) Western blot analysis of Caspase-3, PARP, LC3B and p62 after treated with BKM120 for 48 h. (E) Western blot analysis of p-Akt, Akt and p-mTOR after treatment with BKM120 for 48 h. (F) Representative images of autophagosome puncta in three cell lines treated with BKM120 or/and HCQ for 24 h. Scale bars, 20 ��m. (G) Quantification of autophagosome puncta positive cells (> 10 puncta per cell). All data are mean �� SD from three independent experiments; *p

Additional file 1 Supplementary Figure 1. PCa pathology grading diagnosis by histology observation and the expression of AMACR and TP63. A, D HE staining of PCa tissues. B, E Immunostaining of AMACR on PCa tissues. C, F Immunostaining of TP63 on PCa tissues. Bar = 50 μm. Supplementary Figure 2 CNV analysis of different type of cells in PCa tissues. A All clusters in PCa tissues; B Three types of luminal clusters in PCa tissues. Supplementary Figure 3 Highly expressed genes distributed in PCa. A-C Violin plots displaying the expression of highly expressed genes in each luminal cluster across the cell types identified in PCa (from luminal 1 to luminal 3, respectively); D-F Expression levels of highly expressed genes in each luminal cluster plotted onto the UMAP (from luminal 1 to luminal 3, respectively), color key from gray to red indicates relative expression levels from low to high. Supplementary Figure 4 GO enrichment of differentially expressed genes (DEGs) of each luminal cluster analyzed by pairwise comparison. A, B The enriched GO terms for DEGs between type 1 and type 2 luminal cells; C, D The enriched GO terms for DEGs between type 1 and type 3 luminal cells; E, F The enriched GO terms for DEGs between type 2 and type 3 luminal cells. Supplementary Figure 5 Clustering heatmap demonstrating the correlation between PCa status and the marker gene expression of each luminal cluster using TCGA data. Supplementary Figure 6 Clustering heatmap demonstrating the correlation between PCa status and the marker gene expression of subgroup 1–4 using TCGA data. Supplementary Figure 7 Clinical correlations of 6-gene set from subgroup 5 marker genes were analyzed with their expression patterns in PCa patients from TCGA. A ROC analysis for 6-gene set from subgroup 5 marker genes in distinguishing normal prostate from cancerous prostate; B Kaplan-Meier analysis predicting recurrence-free rate of PCa patients based on the expression changes of 6-gene set from subgroup 5 marker genes. Supplementary Figure 8 Heatmap showing different distinguishing abilities of subgroup 5 marker genes in patients with various pathology gradings. Supplementary Figure 9 ROC analysis of reported candidate marker genes for PCa diagnosis.

Additional file 7: Supplementary Table 1. The IC50 values and RI values of NSCLC parental cells and CDDP resistant cells for 72 h. Supplementary Table 2 Antibody information. Supplementary Table 3 Primer Sequences

In the present study, a series of twelve thiazolyl hydrazone derivatives of 1-indanone was synthesized and characterized by various spectroscopic techniques such as UV-Visible, NMR, IR and Mass Spectrometry. All the synthesized target compounds were subjected to MTT assay for cytotoxicity screening and evaluation of their anti-cancer activity on various cell lines of human cancer including glioblastoma (SNB-19), prostate cancer (PC-3), Lung cancer (NCI-H460), human ovarian carcinoma (SK-OV-3 and IGROV-1), human leukemia (K-562) and human colon cancer(HCT116).Three synthesized compounds showed promising anti-cancer activity against the colon cancer cell HCT 116 cells with IC50 ranging from 1.25and#177;0.02 to 5.04and#177;0.2 and#181;M. On the other hand all the compounds didn’t show cytotoxic activity against other forms of human cancer cells.