Feifei Li

Breast cancer is the most common malignancy and ranks second among the causes of tumor‑associated death in females. The recurrence and drug resistance of breast cancer are intractable due to the presence of breast cancer stem cells (BCSCs), which are adequate to initiate tumor formation and refractory to conventional remedies. Runt‑related transcription factor 2 (RUNX2), a pivotal transcription factor in mammary gland and bone development, has also been related to metastatic cancer and BCSCs. State‑of‑the‑art research has indicated the retention of RUNX2 expression in a more invasive subtype of breast cancer, and in particular, triple‑negative breast cancer development and drug resistance are associated with estrogen receptor signaling pathways. The present review mainly focused on the latest updates on RUNX2 in BCSCs and their roles in breast cancer progression and drug resistance, providing insight that may aid the development of RUNX2‑based diagnostics and treatments for breast cancer in clinical practice.

Longitudinal studies have indicated the pivotal role of natural killer cells (NKs) in the elimination of certain infections and malignancies. Currently, perinatal blood (PB) and cord blood (CB) have been considered with promising prospective for autogenous and allogeneic NKs transplantation, yet the similarities and differences at the biological and molecular levels are largely obscure. We isolated mononuclear cells (MNCs) from PB and CB, and compared the biological phenotypes of resident NKs by flow cytometry and cell counting. Then, we turned to our well-established "3ILs" strategy and co-culture for NK cell activation and cytotoxicity analyses, respectively. Finally, with the aid of transcriptomic analyses, we further dissected the signatures of PB-NKs and CB-NKs. CB-NKs revealed superiority in cellular vitality over PB-NKs, together with variations in subpopulations. CB-NKs showed higher cytotoxicity over PB-NKs against K562 cells. Furthermore, we found both NKs revealed multifaceted conservations and differences in gene expression profiling and genetic variations, together with gene subsets and signaling pathway. Collectively, both NKs revealed multifaceted similarities and diverse variations at the cellular and transcriptomic levels. Our findings would benefit the further exploration of the biological and transcriptomic properties of CB-NKs and PB-NKs, together with the development of NK cell-based cytotherapy.

Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer im-munosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale ap-plication. Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations. The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25+ memory-like NK cell subset. Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future.

Breast cancer remains the most common malignancy in women and constantly threatens the lives of patients worldwide. State-of-the-art renewal has indicated the involvement of RUNX-associated transcription factor 2 (RUNX2) in tumorigenesis and cancer progression, yet the detailed information during breast cancer is largely obscure. Herein, we took advantage of breast cancer cell lines and in vivo tumorigenicity test as well as multifaceted phenotypic analyses (e.g., RNA-sequencing, ChIP and qRT-PCR assay) to verify the pathogenic mechanism of RUNX2 in triple negative breast cancer aggressiveness and chemoresistance. Strikingly, the proliferation, migration, invasion and chemoresistance of resistant cell lines in triple negative breast cancer was effectively suppressed by RUNX2 silencing, and the in vivo tumorigenicity was significantly weakened as well. Furthermore, with the aid of transcriptomic and bioinformatic analyses, we found MMP1 was highly expressed in triple negative breast cancer (TNBC) and showed a strong correlation with the poor prognosis of the patients, which was consistent with the expression pattern of RUNX2. Finally, by conducting ChIP and qRT-PCR assessment, we verified that RUNX2 functioned via directly binding to the specific motifs in the promoter of MMP1 and thus activating the transcriptional process. Collectively, our data demonstrated the facilitating effect of RUNX2 during triple negative breast cancer progression by directly orchestrating the expression of MMP1, which supplied overwhelming new references for RUNX2-MMP1 axis serving as a novel candidate for breast cancer diagnosis and treatment.