Background Triple-receptor negative breast cancer (TNBC) is an aggressive breast tumor subtype that generally has a poor prognosis. This study aimed to investigate the role and regulatory mechanisms of Zinc finger MIZ-type containing 2 (ZMIZ2) in relation to TNBC. Methods Based on data from The Cancer Genome Atlas (TCGA), the expression of ZMIZ2 in different subtypes and its correlation with androgen receptor (AR) were analyzed, and a regulatory mechanism network was constructed. The expression and prognostic value of ZMIZ2 in clinical TNBC tissue samples were also investigated. Furthermore, in vitro studies were conducted to investigate the effects of ZMIZ2 knockdown on the malignant behaviors of TNBC cells and target gene expression. Results Based on TCGA data, ZMIZ2 was found to be significantly upregulated in TNBC tissues and its expression was negatively correlated with AR expression. Key relationships, such as the ZMIZ2-CCL5, ZMIZ2/AR-MCM3, ZMIZ2/AR-E2F4, and the ZMIZ2/AR-DHX38 were identified, which were enriched in NOD-like receptor signaling pathway/toll-like receptor signaling pathway, DNA replication, cell cycle, and spliceosome, respectively. Moreover, ZMIZ2 was upregulated in clinical breast cancer tissues and its high expression was correlated with the poor prognosis of TNBC patients. Furthermore, ZMIZ2 expression was increased in breast cancer cells, and a knockdown of ZMIZ2 inhibited MDA-MB-231 cell proliferation, migration, and invasion, induced cell cycle arrest in the G1 phase, and promoted cell apoptosis. Furthermore, ZMIZ2 knockdown inhibited the mRNA and protein expression of CCL5, MCM3, E2F4, and DHX38. Conclusion Our findings reveal that ZMIZ2 is upregulated in TNBC tissues and is associated with its poor prognosis. ZMIZ2 may promote TNBC progression by promoting the expression of its target genes and affecting the corresponding pathways. Consequently, ZMIZ2 may serve as a promising target for future TNBC treatments.
Breast cancer is one of the most frequently diagnosed cancers amongst women; however, there is currently no effective treatment. Natural compounds are considered to contribute to cancer prevention and have a pivotal role in modulating apoptosis. Rosmanol is a phenolic diterpene compound with antioxidant and anti-inflammatory properties.In the present study, the effects of Rosmanol on breast cancer cell proliferation/apoptosis were investigated, and it was demonstrated that it inhibited the proliferation of MCF-7 and MDA-MB 231 cells but did not have a significant effect on normal human breast MCF-10A cells. In addition, the apoptotic process was accelerated by Rosmanol, through mitochondrial pathways and reactive oxygen species (ROS) production caused by DNA damage, which function further demonstrated by the attenuation and addition of the ROS inhibitor, N-acetyl-cysteine. It was also demonstrated that Rosmanol accelerated cell apoptosis, and arrested breast cancer cells in the S phase. Moreover, Rosmanol inhibited proliferation and promoted apoptosis of cancer cells via the inhibition of ERK and STAT3 signals, attributable to the increase in p-p38, the overexpression of protein inhibitor of activated STAT3, and the decrease in PI3K/AKT, ERK and JAK2/STAT3.
Background: There is a higher possibility for rheumatoid arthritis (RA) recurrence if patients have subclinical synovitis. Seven-joint ultrasonic score (US7 score) allows an accurate detection of subclinical synovitis, but its predictive role in the recurrence of RA patients in remission is uncertain. Objectives: The goal of this study was to explore the role of US7 score in predicting the recurrence of RA patients with disease in clinical remission. Patients and Methods: Totally, 186 RA patients in clinical remission were recruited and their demographic and clinicobiologic characteristics were collected. The US7 score and disease activity score in 28 joints (DAS28) were recorded as baseline indicators for a 1-year follow-up. Patients were divided into the recurrence group and non-recurrence group according to their recurrent results. The clinical indicators and US7 scores before the follow-up were compared and analyzed between the two groups. Kaplan-Meier and univariate COX regression analysis were used to analyze the effect of US7 score on the recurrence of RA. Receiver-operating characteristics (ROC) curves were established to evaluate the predictive accuracy of DAS 28 and US7 score for the outcome of RA. Results: Of the 186 RA patients, 55.9% received conventional disease-modifying antirheumatic drugs (cDMARDs) and 44.1% received biologic disease-modifying antirheumatic drugs (bDMARDs). Totally, 60 patients (32.3%) suffered from recurrence and were included in the recurrence group, and the remaining 126 patients were included in the non-recurrence group. The recurrence rate of patients without subclinical synovitis (10.26%) was lower than that of patients with subclinical synovitis (48.15%, χ2 = 27.556, P < 0.001). US7 score was associated with an increased risk of recurrence in RA patients after successful treatment (P < 0.001, hazard ratio = 1.363, 95% CI = 1.247 - 1.488). The area under the curve of the prediction model with combined US7 score and DAS 28 was higher (0.904) compared to that of US7 score or DAS 28 (P < 0.05). Conclusion: The US7 score is capable of predicting the recurrence of RA patients because of its advantages in identifying subclinical synovitis. The combined model of DAS28 and US7 score was accurate for predicting the recurrence of RA patients in clinical remission.
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