Supplementary Figure S3 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer

Somatic mutations across JMJD1 proteins.</p

Supplementary Figure S4 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer

Reaction rate of JMJD1A in dependence of the oxygen concentration.</p

Supplementary Figure S1 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer

Relationship between HR and the three JMJD1 proteins.</p

Supplementary Figure S2 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer

JMJD1 gene alteration frequencies.</p

Supplementary Table S1 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer

Correlation between JMJD1 mRNA levels in tumors.</p

DataSheet_1_Promotion of colorectal cancer by transcription factor BHLHE40 involves upregulation of ADAM19 and KLF7.pdf

BHLHE40 is a transcription factor, whose role in colorectal cancer has remained elusive. We demonstrate that the BHLHE40 gene is upregulated in colorectal tumors. Transcription of BHLHE40 was jointly stimulated by the DNA-binding ETV1 protein and two associated histone demethylases, JMJD1A/KDM3A and JMJD2A/KDM4A, which were shown to also form complexes on their own and whose enzymatic activity was required for BHLHE40 upregulation. Chromatin immunoprecipitation assays revealed that ETV1, JMJD1A and JMJD2A interacted with several regions within the BHLHE40 gene promoter, suggesting that these three factors directly control BHLHE40 transcription. BHLHE40 downregulation suppressed both growth and clonogenic activity of human HCT116 colorectal cancer cells, strongly hinting at a pro-tumorigenic role of BHLHE40. Through RNA sequencing, the transcription factor KLF7 and the metalloproteinase ADAM19 were identified as putative BHLHE40 downstream effectors. Bioinformatic analyses showed that both KLF7 and ADAM19 are upregulated in colorectal tumors as well as associated with worse survival and their downregulation impaired HCT116 clonogenic activity. In addition, ADAM19, but not KLF7, downregulation reduced HCT116 cell growth. Overall, these data have revealed a ETV1/JMJD1A/JMJD2A→BHLHE40 axis that may stimulate colorectal tumorigenesis through upregulation of genes such as KLF7 and ADAM19, suggesting that targeting this axis represents a potential novel therapeutic avenue.</p

Discrimination and validation of nomogram for predicting LNM in patients with DCIS-MI.

The ROC curves of the nomogram for predicting LNM in the training cohort (A), validation cohort (B) and test cohort (C). Calibration plots for the nomogram in the training cohort (D), validation cohort (E) and test cohort (F). (AUC, area under the curve; 95%CI, 95% confidence interval).</p

Nomogram predicting regional LNM in patients with DCIS-MI based on training set.

Note: The first row is the point assignment for each variable. Rows 2–5 indicate the variables included in the nomogram. For an individual patient, each variable is assigned a point value based on the histopathological characteristics. The points for each variable were summed and located on the total point line. And then, the bottom line shows the probability of the patient having regional LNM.</p

S3 Data -

BackgroundDuctal carcinoma in situ with microinvasion (DCIS-MI) is a special type of breast cancer. It is an invasive lesion less than 1.0 mm in size related to simple ductal carcinoma in situ (DCIS). Lymph node metastasis (LNM) in DCIS-MI often indicates a poor prognosis. Therefore, the management of lymph nodes plays a vital role in the treatment strategy of DCIS-MI. Since DCIS-MI is often diagnosed by postoperative paraffin section and immunohistochemical detection, to obtain the best clinical benefits for such patients, we aim to establish and verify a nomogram to predict the possibility of lymph node metastasis in DCIS-MI patients and help preoperative or intraoperative clinical decision-making.MethodsA retrospective analysis of patients with DCIS-MI in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019 was performed. The study cohort was randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The risk factors were determined by univariate and multivariate logistic regression analyses in the training cohort, and a nomogram was constructed. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram in the training set and validation set. An independent data cohort was obtained from the Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB) for external validation.ResultsThis study included 3951 female patients from SEER with DCIS-MI, including 244 patients with regional lymph node metastasis, accounting for 6.18% of the total. An independent test set of 323 patients from SJTU-BCDB was used for external validation. According to the multifactorial logistic regression analysis results, age at diagnosis, ethnicity, grade, and surgical modality were included in the prediction model. The areas under the ROC curves (AUCs) were 0.739 (95% CI: 0.702~0.775), 0.732 (95% CI: 0.675~0.788), and 0.707 (95%CI: 0.607–0.807) in the training, validation and external test groups, suggesting that the column line graphs had excellent differentiation. The calibration curves slope was close to 1, and the model’s predicted values were in good agreement with the actual values. The DCA curves showed good clinical utility.ConclusionIn this study, we constructed accurate and practical columnar maps with some clinical benefit to predict the likelihood of lymph node metastasis in patients with postoperatively diagnosed DCIS-MI and provide a reference value for specifying treatment strategies.</div

Data_Sheet_1_Genome Sequence, Assembly, and Characterization of the Antagonistic Yeast Candida oleophila Used as a Biocontrol Agent Against Post-harvest Diseases.xlsx

Candida oleophila is an effective biocontrol agent used to control post-harvest diseases of fruits and vegetables. C. oleophila I-182 was the active agent used in the first-generation yeast-based commercial product, Aspire®, for post-harvest disease management. Several action modes, like competition for nutrients and space, induction of pathogenesis-related genes in host tissues, and production of extracellular lytic enzymes, have been demonstrated for the biological control activity exhibited by C. oleophila through which it inhibits post-harvest pathogens. In the present study, the whole genome of C. oleophila I-182 was sequenced using PacBio and Illumina shotgun sequencing technologies, yielding an estimated genome size of 14.73 Mb. The genome size is similar in length to that of the model yeast strain Saccharomyces cerevisiae S288c. Based on the assembled genome, protein-coding sequences were identified and annotated. The predicted genes were further assigned with gene ontology terms and clustered in special functional groups. A comparative analysis of C. oleophila proteome with the proteomes of 11 representative yeasts revealed 2 unique and 124 expanded families of proteins in C. oleophila. Availability of the genome sequence will facilitate a better understanding the properties of biocontrol yeasts at the molecular level.</p