The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of development and in adulthood. Importantly, HMGA2 is re-expressed in nearly all human malignancies, where it promotes tumorigenesis by multiple mechanisms. HMGA2 increases cancer cell proliferation by promoting cell cycle entry and inhibition of apoptosis. In addition, HMGA2 influences different DNA repair mechanisms and promotes epithelial-to-mesenchymal transition by activating signaling via the MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFkB, and STAT3 pathways. Moreover, HMGA2 supports a cancer stem cell phenotype and renders cancer cells resistant to chemotherapeutic agents. In this review, we discuss these oncogenic roles of HMGA2 in different types of cancers and propose that HMGA2 may be used for cancer diagnostic, prognostic, and therapeutic purposes.
Evading immune destruction is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3 + T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA-DR -CD33 + MDSCs in peripheral blood is about 10-fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA-DR -CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient-derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patientderived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC.
BACH1 is overexpressed in prostate cancer. Because this promotes invasion and migration, it may facilitate metastasis of prostate cancer. Thus, BACH1 is a potential therapeutic target for metastatic prostate cancer. BACH1 silencing therapy can be considered as a novel and effective adjuvant in prostate cancer targeted therapies.
Purpose Altered expression of microRNAs (miRNAs) is indicated strongly in colorectal cancer (CRC). This study aims to evaluate the inhibitory role of miR‐193a‐5p on epithelial‐mesenchymal transition markers in CRC lines. The cellular effects and potential mechanisms of miR‐193a‐5p were also examined. Methods Quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) was performed to determine the expression of miR‐193a‐5p in three CRC cell lines (HCT‐116, SW‐480, and HT‐29) and its impact on metastasis‐related genes ( vimentin and CXCR4) before and after mimic transfection. Of those, the cell line with the highest changes was selected for the next upcoming experiments such as wound‐healing assay, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), and annexin‐V staining tests. Results Our results revealed that miR‐193a‐5p was significantly downregulated in three CRC cell lines and that HT‐29 displayed the most decrease ( P < 0.0001). The restoration of miR‐193a‐5p in human HT‐29 cell line inhibited cell migration. But, miR‐193a‐5p transfection did not affect cell viability and had no significant effect on apoptosis induction. Also, the quantitative RT‐PCR analysis of miR‐193a‐5p mimic transfected cells revealed a significant increase in miR‐193a‐5p messenger RNA (mRNA) expression level ( P < 0.0001) with reduction of vimentin and CXCR4 mRNA expression levels in HT‐29 cell line ( P < 0.01 and < 0.05, respectively). Conclusion Our results indicated that miR‐193a‐5p acts as a tumor suppressor miRNA and its downregulation plays an important role in metastasis via upregulation of metastasis‐related genes in CRC. Therefore, it can be considered as a potential therapeutic target for applying in CRC management in the future.
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