LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with fewer treatment options than other types of invasive breast cancer due to the loss of the estrogen, progesterone receptors and low levels of the HER2 protein, resulting in a poor prognosis for these patients. Here, we found that the expression of the lncRNA, ZFAS1, was significantly downregulated (∼3.0-fold) in blood samples of TNBC patients (n=40) compared to matched healthy controls (n=40). Functionally, silencing of ZFAS1 promoted cell proliferation and colonization of human MDA-MB-231 TNBC cells by inhibiting the expression levels of the cyclin-dependent kinase (CDK) inhibitors p21 (CDKN1A) and p27 (CDKN1B) compared to the scrambled siRNA control cells. Further, we found that downregulation of ZFAS1 led to decreased protein levels of the epithelial markers, E-cadherin, Claudin-1, and Zo-1, with increased protein levels of the mesenchymal markers, Slug and ZEB1. In addition, by utilizing the bioinformatic tools such as RAID v2.0 (RNA Interactome Database Version 2.0), AnnoLnc (Annotate human lncRNA database), and GEPIA (Gene Expression Profiling Interactive Analysis), we identified a strong negative correlation between ZFAS1 and signal transducer and activator of transcription 3 (STAT3) gene expression (R = -0.11, p-value = 0.0002). Further, we observed that decreased ZFAS1 expression significantly (p < 0.05) increased STAT3 and phosphorylated STAT3 (at Ser727 residue) protein levels in TNBC cells. The composite data indicate that ZFAS1 may function as a tumor-suppressor lncRNA with potential as a diagnostic/prognostic marker and may offer a new target for the treatment of TNBC patients.

Diagnostic value of bone marrow aspiration and biopsy in routine hematology practice.

BACKGROUND: The bone marrow is frequently involved in variety of cases presenting with hematological and non-hematological disorders, which are diagnosed by two separate but interrelated techniques such as bone marrow aspiration (BMA) and bone marrow biopsy (BMB). AIM: This study was aimed to assess the diagnostic value of the BMA and BMB and role of both the procedures to reach final diagnosis when done simultaneously. SETTINGS AND DESIGN: It was a prospective study. The findings of BMA smears were correlated with BMB sections and data obtained was analysed. MATERIALS AND METHODS: BMA and BMB were performed on 50 patients. Criteria of inclusion included the main indications for performing this procedure, the availability of full medical records and patient consent. The patients had a male to female sex ratio of 1.6:1 and a wide age range from 4 years to 74 years. RESULTS: In the present study, the main indications for bone marrow examination were categorized. Out of 50 cases studied, in 23 cases, a strong positive correlation between BMA and BMB was noted. However, it was found that in the cases of aplastic anaemia, different phases of myeloproliferative neoplasm (MPN), multiple myeloma, tubercular granulomas and hemato-lymphoid neoplasm, involvement of the marrow was detected better in bone marrow biopsies. CONCLUSION: The study concludes that preparations of aspirate and trephine biopsy are easy, rapid and complementary to each other in majority of the lesions. The advantage of both the procedures done together enabled us to study the cytomorphology of the cells along with the pattern of distribution of the cells depending on the cases, hence help in making the diagnosis accurately.