HIST1H1B Promotes Basal-Like Breast Cancer Progression by Modulating CSF2 Expression.

BACKGROUND: Basal-like breast cancer (BLBC) is associated with a poor clinical outcome; however, the mechanism of BLBC aggressiveness is still unclear. It has been shown that a linker histone functions as either a positive or negative regulator of gene expression in tumors. Here, we aimed to investigate the possible involvement and mechanism of HIST1H1B in BLBC progression. EXPERIMENTAL DESIGN: We analyzed multiple gene expression datasets to determine the relevance of HIST1H1B expression with BLBC. We employed quantitative real-time PCR, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the expression of HIST1H1B in human breast cancer. We studied the association of HIST1H1B with CSF2 by ChIP assay. Using tumorigenesis assays, we determine the effect of HIST1H1B expression on tumorigenicity of BLBC cells. RESULTS: Here, we show that the linker histone HIST1H1B is dramatically elevated in BLBC due to HIST1H1B copy number amplification and promoter hypomethylation. HIST1H1B upregulates colony-stimulating factor 2 (CSF2) expression by binding the CSF2 promoter. HIST1H1B expression promotes, whereas knockdown of HIST1H1B expression suppresses tumorigenicity. In breast cancer patients, HIST1H1B expression is positively correlated with large tumor size, high grade, metastasis and poor survival. CONCLUSION: HIST1H1B contributes to basal-like breast cancer progression by modulating CSF2 expression, indicating a potential prognostic marker and therapeutic target for this disease.

Metabolic reprogramming in triple-negative breast cancer.

Since triple-negative breast cancer (TNBC) was first defined over a decade ago, increasing studies have focused on its genetic and molecular characteristics. Patients diagnosed with TNBC, compared to those diagnosed with other breast cancer subtypes, have relatively poor outcomes due to high tumor aggressiveness and lack of targeted treatment. Metabolic reprogramming, an emerging hallmark of cancer, is hijacked by TNBC to fulfill bioenergetic and biosynthetic demands; maintain the redox balance; and further promote oncogenic signaling, cell proliferation, and metastasis. Understanding the mechanisms of metabolic remodeling may guide the design of metabolic strategies for the effective intervention of TNBC. Here, we review the metabolic reprogramming of glycolysis, oxidative phosphorylation, amino acid metabolism, lipid metabolism, and other branched pathways in TNBC and explore opportunities for new biomarkers, imaging modalities, and metabolically targeted therapies.

Event-related potentials in adolescents with combined ADHD and CD disorder: a single stimulus paradigm.

Some studies of the event-related potentials demonstrated a reduction of the voluntary component P3 (P300 or P3b) in youngsters with the attention deficit/hyperactivity disorder (ADHD) or in conduct disorders (CD), and a reduction of the automatic processing component, mismatch negativity, in patients with both ADHD and CD (ADHD+CD). Recently, a passive auditory P3 potential has been elicited by a single stimulus. We therefore tried this potential study in 20 healthy subjects and 20 teenagers with ADHD+CD to search for further evidence of the altered automatic cerebral processing in the latter. Subjects also answered a self-report Dimensional Assessment of Personality Pathology (DAPP). The patient group scored significantly higher on most DAPP traits that reflect problems of emotion control, showed significantly prolonged P2, N2, and P3, and reduced P3. In all subjects Stimulus Seeking was positively correlated with P3 latencies at Fz, Cz, and Pz, and with P3 amplitude at Cz. This study suggests that youngsters with ADHD+CD had pronounced emotion dysregulation, and prominent deficit in passive attention, as reflected by the automatic processing of auditory stimuli.