Biomedical Indicators of Patients with Non-Puerperal Mastitis: A Retrospective Study.

BACKGROUND: Non-puerperal mastitis (NPM), a recurrent chronic inflammation of non-lactating breast, often proves tremendous difficulty in treatment, and it may give rise to its complicated symptoms and unclear etiology. Furthermore, the clinical morbidity rate of NPM has been increasing in recent years. METHODS: Overall, 284 patients diagnosed with NPM were consecutively recruited as cases in this study, and patients with benign breast disease (n = 1128) were enrolled as control. The clinical, biomedical, and pathological indicators were analyzed. Univariate and multivariate logistic analysis were used to distinguish risks between NPM and benign breast mass patients. Furthermore, according to the pathological characteristics, the patients of NPM were classified into two subgroups: mammary duct ectasia (MDE) and granulomatous lobular mastitis (GLM). The differences of biomedical indicators between MDE and GLM groups were also analyzed. RESULTS: Compared with benign breast mass group, the level of high-density lipoprotein (HDL-C) significantly decreased, while lipoprotein(a) (Lp(a)) and blood glucose (GLU) both increased in NPM group. According to univariate and multivariate logistic analysis, the onset age and HDL-C were generally decreased, while Lp(a) and GLU were increased in NPM group. The onset age, HDL-C, Lp(a), and GLU were modeled to distinguish NPM and benign breast mass. Significant differences were also observed between MDE and GLM patients in biomedical indicators, such as lipoprotein(a) (Lp(a)), lactate dehydrogenase (LDH), creatine kinase (CK), total cholesterol (TC), and so on. CONCLUSIONS: Our results indicated for the first time that biomarkers were associated with NPM. The biomedical indicators involved in lipid metabolism might be important factors in the development and treatment of NPM. In addition, MDE and GLM are two diseases with different inflammatory states of NPM. These findings would be helpful for a better understanding of NPM and give us some insights to develop new diagnostic and therapeutic strategies.

Oncogenic action of the exosome cofactor RBM7 by stabilization of CDK1 mRNA in breast cancer.

RNA exosome can target the specific RNAs for their processing/degradation by distinct exosome cofactors. As a key component in exosome cofactors, RNA binding motif protein 7 (RBM7) shows the binding specificity for uridine-rich sequences in mRNAs via its RNA recognition motifs. However, the specific function of RBM7 in human breast cancer remains unclear. In vitro, experiments revealed that knockdown of RBM7 dramatically inhibited breast cancer cell proliferation, while inducing G1 cell cycle arrest; the opposite was true when RBM7 was overexpressed. Meanwhile, experiments in vivo confirmed the oncogenic function of RBM7 in breast cancer. RNA sequencing and the following pathway analysis found that cyclin-dependent kinase1 (CDK1) was one of the main gene regulated by RBM7. Overexpression of RBM7 increased CDK1 expression, while RBM7 knockdown decreased it. RIP assays additionally found that RBM7 bound directly to CDK1 mRNA. It was also showed that RBM7 could directly bind to the AU-rich elements (AREs) in 3'-UTR of CDK1 mRNA, which contributed to the stability of CDK1 mRNA by lengthening its half-life. More importantly, the oncogenic activity reduced by knockdown of RBM7 could be rescued by overexpression of CDK1 both in vitro and in vivo, but mutant CDK1 failed. All the evidences implied RBM7 promoted breast cancer cell proliferation by stabilizing CDK1 mRNA via binding to AREs in its 3'-UTR. As we knew, it was the first attempt to connect the RNA exosome to the tumor development, providing new insights into the mechanisms of RNA exosome-linked diseases.

Correction to: The RNA binding protein RBMS3 inhibits the metastasis of breast cancer by regulating Twist1 expression.

In the original publication of this article [1], the molecular weight of RBMS3 was incorrectly noted as 38 KDa within Fig 1A, Fig 2A and Fig 2B. The figures have been updated to list the correct molecular weight of RBMS3 as 41 KDa.

TCDD-Inducible Poly-ADP-Ribose Polymerase (TIPARP), A Novel Therapeutic Target Of Breast Cancer.

BACKGROUND: TIPARP (TCDD-inducible poly-ADP-ribose polymerase), a mono-ADP-ribosyltransferase and a transcriptional repressor of aryl hydrocarbon receptor (AHR), was one of the potential therapeutic targets for human cancers identified by CRISPR-Cas9 screens recently. Studies about TIPARP on cancers are scarce till now, most of which just focus on expressions, while the functions have not been widely reported yet. Moreover, the TIPARP prognostic significance and therapeutic value of breast cancer is also uncertain. METHODS: The present study was performed to comprehensively analyze the expression pattern, prognostic effect, potential therapeutic function of TIPARP in breast cancer by pooling all currently available databases online including Oncomine, UALCAN, bc-GenExMiner, Kaplan-Meier Plotter, COSMIC, UCSC Xena, STRING, DAVID and Comparative Toxicogenomics Database. Further, we also performed several cell biology experiments including RT-qPCR, Western blot and CCK-8 in cellular and clinical sample levels to confirm the conclusions from bioinformatics analysis. RESULTS: TIPARP was expressed lower in tumor tissues comparing with normal tissues. Meanwhile, several clinical parameters of breast cancer patients were correlated with TIPARP expression. Further, higher TIPARP expression was related to preferable survival. Moreover, the mutations and DNA methylation of TIPARP might contribute to TIPARP dysregulation in breast cancer. Interactors with TIPARP were significantly enriched in telomere maintenance, telomere organization and mainly participated in pathways in cancer. Finally, several common drugs including metformin were observed to up-regulate the expression of TIPARP. CONCLUSION: TIPARP might act as a preferable prognostic marker of breast cancer through multiple biological processes such as DNA methylation, mutation as well as pathway related to telomere and so on. TIPARP could be considered as a potential therapeutic target for breast cancer. However, large-scale and comprehensive research is needed to clarify our results.

The RNA binding protein RBMS3 inhibits the metastasis of breast cancer by regulating Twist1 expression.

BACKGROUND: Metastasis remains the biggest obstacle for breast cancer treatment. Therefore, identification of specific biomarker of metastasis is very necessary. The RNA binding protein 3 (RBMS3) acts as a tumor suppressor in various cancers. Whereas, its role and underlying molecular mechanism in breast cancer is far from elucidated. METHODS: Quantitative real-time PCR and western blots were carried out to determine the expression of RBMS3 in breast cancer cells and tissues. Transwell and in vivo metastasis assay were conducted to investigate the effects of RBMS3 on migration, invasion and metastasis of breast cancer cells. Transcriptome sequencing was applied to screen out the differential gene expression affected by RBMS3. RNA immunoprecipitation assay combined with luciferase reporter assay were performed to explore the direct correlation between RBMS3 and Twist1 mRNA. RESULTS: RBMS3 was downregulated in breast cancer and ectopic expression of RBMS3 contributed to inhibition of cell migration, invasion in vitro and lung metastasis in vivo. Furthermore, RBMS3 negatively regulated Twsit1 expression via directly binding to 3'-UTR of Twist1 mRNA, and thereby decreased Twist1-induced expression of matrix metalloproteinase 2 (MMP2). Additionally, Twist1-induced cell migration, invasion and lung metastasis could be reversed by the upregulation of RBMS3. CONCLUSIONS: In summary, our study revealed a novel mechanism of the RBMS3/Twsit1/MMP2 axis in the regulation of invasion and metastasis of breast cancer, which may become a potential molecular marker for breast cancer treatment.

RBMS2 inhibits the proliferation by stabilizing P21 mRNA in breast cancer.

BACKGROUND: RNA binding proteins (RBPs) play an important role in regulating the metabolism of target RNAs. Aberrant expression of RBPs plays a vital role in the initiation and development of many cancers. The RBM family, which has the conserved RNA binding motif RNP1 and RNP2, shares the similar function in RNA processing and RBMS2 is a member of them. P21, also named CDKN1A, promotes cell cycle arrest and plays an important role in halting cell proliferation. In our study, we identified RBMS2 as a tumor suppressor in breast cancer. It inhibited the proliferation of breast cancer by positively regulating the stability of P21 mRNA in posttranscriptional way. METHODS: TCGA was used to identify differentially expressed RBPs in breast cancer. The effect of RBMS2 on breast cancer proliferation was evaluated in vitro using CCK-8 assays, colony formation assays and cell-cycle assays and the in vivo effect was investigated using a mouse tumorigenicity model. The main pathway and genes regulated by RBMS2 was detected by RNA sequencing. The RNA immunoprecipitation combined with dual-luciferase reporter assay were conducted to testify the direct binding between RBMS2 and P21. Rescue assay was used to detect P21 as the main target of RBMS2. RESULTS: The expression of RBMS2 was lower in breast cancer compared with normal tissues and was a favorable biomarker in breast cancer. RBMS2 inhibited the proliferation of breast cancer and P21 was the main target of RBMS2. RBMS2 stabilized the mRNA of P21 by directly binding to the AU-rich element of 3'-UTR region. Anti-proliferation activity induced by overexpression of RBMS2 was rescued by interfering with the expression of P21. CONCLUSION: In conclusion, RBMS2 acted as a tumor suppressor in breast cancer and positively regulated the expression of P21 by stabilizing its mRNA.