Epithelial–mesenchymal transition (EMT) contributes to tumor invasion and metastasis in many cancers and correlates highly with the acquisition of cancer stem cell (CSC) characteristics. EMT also correlates with changes in specific microRNAs (miRNAs) that have already been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. Here, we show that miR‐7, which was downregulated in breast CSCs (BCSCs) isolated from the human MCF‐7 and MDA‐MB‐231 cell lines, inhibited cell invasion and metastasis, decreased the BCSC population and partially reversed EMT in MDA‐MB‐231 cells by directly targeting the oncogene, SETDB1. The conspicuous epigenetic transition induced by miR‐7 overexpression was found not only in MDA‐MB‐231 cells but also in BCSC xenograft tumors. MiR‐7 inhibited the metastasis of BCSCs in lungs, kidneys, and adrenal glands of NOD/SCID mice. ChIP‐polymerase chain reaction result suggested that the SETDB1 induced STAT3 expression by binding to the promoter of STAT3. MiR‐7‐mediated downregulation of SETDB1 resulted in the suppression of STAT3, which led to the downregulation of c‐myc, twist, and mir‐9. In addition, the downregulation of miR‐7 in BCSCs may be indirectly attributed to lincRNA HOTAIR by modulating the expression of HoxD10 that promotes the expression of miR‐7. These findings demonstrate that miR‐7 was a tumor suppressor and that the overexpression of miR‐7 might serve as a good strategy for treating highly invasive breast cancer. Stem Cells 2014;32:2858–2868

Background: Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking.

Background: PLEKHA5 has previously been identified as a novel molecule implicated in melanoma brain metastasis, a disease that continues to portend a poor prognosis. The aim of this study was to further investigate the functional role of PLEKHA5 in disseminated melanoma.Methods: The impact of PLEKHA5 on proliferation and tumor growth was examined in vitro and in melanoma xenograft models, including brain‐tropic melanomas (melanomas tending to disseminate to the brain). In vitro loss‐ and gain‐of‐function studies were used to explore the underlying mechanisms of PLEKHA5‐mediated tumor growth and the crosstalk between PLEKHA5 and PI3K/AKT/mTOR or MAPK/ERK signaling. The clinical relevance of PLEKHA5 dysregulation was further investigated in a cohort of matched cranial and extracranial melanoma metastases.Results: PLEKHA5 stable knockdown negatively regulated cell proliferation by inhibiting the G₁‐to‐S cell cycle transition, which coincided with upregulation of the cell cycle regulator PDCD4. Conversely, ectopic PLEKHA5 expression exhibited the inverse effect. PLEKHA5 knockdown significantly inhibited tumor growth, whereas its overexpression upregulated the growth of tumors, which was induced by cranial and subcutaneous inoculation of cells in nude mice. PLEKHA5 modulation affected PDCD4 protein stability and was coupled with changes in PI3K/AKT/mTOR pathway signaling. High PDCD4 expression in cerebral specimens was associated with better overall survival.Conclusions: This study further supports the role of PLEKHA5 as a regulator of melanoma growth at distant sites, including the brain. Furthermore, the results highlight the significance of PDCD4 dysregulation in disseminated melanoma and implicate PDCD4 as a possible causal link between PLEKHA5 and cell proliferation and growth.

Breast cancer is the leading cancer diagnosed in women globally, with brain metastasis emerging as a major cause of death, particularly in human epidermal growth factor receptor 2 positive and triple-negative breast cancer subtypes. Comprehensive understanding of the molecular foundations of central nervous system metastases is imperative for the evolution of efficacious treatment strategies. Lipocalin-2 (LCN2), a secreted iron transport protein with multiple functions, has been linked to the progression of breast cancer brain metastasis (BCBM). In primary tumors, LCN2 promotes the proliferation and angiogenesis of breast cancer cells, triggers the epithelial-mesenchymal transition, interacts with matrix metalloproteinase-9, thereby facilitating the reorganization of the extracellular matrix and enhancing cancer cell invasion and migration. In brain microenvironment, LCN2 undermines the blood-brain barrier and facilitates tumor seeding in the brain by modulating the behavior of key cellular components. In summary, this review meticulously examines the fuel role of LCN2 in BCBM cascade, and investigates the potential mechanisms involved. It highlights the potential of LCN2 as both a therapeutic target and biomarker, indicating that interventions targeting LCN2 may offer improved outcomes for patients afflicted with BCBM.

Lycium barbarum extracts have been shown to be effective in male reproductive protection and male infertility. However, its role in enhancing testicular function, such as testosterone synthesis, and the potential mechanism remain to be understood. To elucidate the effects of Lycium barbarum glycopeptide (LbGp) on testosterone synthesis, we isolated primary Leydig cells (LCs) from testes and performed RNA sequencing (RNA seq) on LCs treated with LbGp. In this study, we demonstrated that LbGp promoted testosterone synthesis in LCs both in vivo and in vitro. We also demonstrated that LbGp elevated adenosine 5′-triphosphate (ATP) synthesis and cell proliferation by enhancing glucose metabolism. Mechanistically, LbGp upregulated testosterone synthesis by suppressing TGF-β pathway and enhancing the expression of steroidogenic genes: Cyp11a1, Hsd3b1, Hsd17b3, Star, and Sf-1. These findings indicate that LbGp plays an important role in enhancing testicular function and promoting testosterone synthesis.