SPRY4‐intronic transcript 1 has been found in several kinds of cancers, but the role of SPRY4‐IT1 in breast cancer stem cells has not been studied. We investigated whether SPRY4‐IT1 is involved in the promotion of breast cancer stem cells (BCSCs). We used qRT‐PCR to detect the expression of SPRY4‐IT1 in MCF‐7 cells and MCF‐7 cancer stem cells (MCF‐7 CSCs). The effects of SPRY4‐IT1 on the proliferation and renewal ability of breast cancer cells were investigated by in vitro and in vivo assays (ie in situ hybridization, colony formation assay, sphere formation assay, flow cytometry assay, western blotting, xenograft model and immunohistochemistry). The mechanism of SPPRY4‐IT1 as a ceRNA was studied by a dual‐luciferase reporter assay and bioinformatic analysis. In our study, SPRY4‐IT1 was up‐regulated in MCF‐7 CSCs compared with MCF‐7 cells, and high SPRY4‐IT1 expression was related to reduced breast cancer patient survival. Furthermore, SPRY4‐IT1 overexpression promoted breast cancer cell proliferation and stemness in vitro and in vivo. In addition, SPRY4‐IT1 knockdown suppressed BCSC renewal ability and stemness maintenance in vivo and in vitro. The dual‐luciferase reporter assays indicated that SPRY4‐IT1 as a sponge for miR‐6882‐3p repressed transcription factor 7‐like 2 (TCF7L2) expression. Taken together, these findings demonstrated that SPRY4‐IT1 promotes proliferation and stemness of breast cancer cells as well as renewal ability and stemness maintenance of BCSCs by increasing the expression of TCF7L2 through targeting miR‐6882‐3p.

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Annexin A2 (ANXA2) is a calcium regulated phospholipid-binding protein. It is expressed in some tumor cells, endothelial cells, macrophages, and mononuclear cells, affecting cell survival and mediating interactions between intercellular and extracellular microenvironment. Aberrant expression of ANXA2 can be used as a potential predictive factor, diagnostic biomarker and therapeutic target in cancer therapy. Investigators used various technologies to target ANXA2 in a preclinical model of human cancers and demonstrated encouraging results. In this review article, we discuss the diagnosis and prognosis latent capacity of ANXA2 in progressive cancers, focus on the exploration of restorative interventions targeting ANXA2 in cancer treatment. Further, we comment on a promising candidate therapy that is conceivable for clinical translation.

Background The tumor microenvironment (TME) plays a critical role in tumorigenesis, development, and therapeutic efficacy. Major advances have been achieved in the treatment of various cancers through immunotherapy. Nevertheless, only a minority of patients have positive responses to immunotherapy, which is partly due to conditions of the immunosuppressive microenvironment. Therefore, it is essential to identify prognostic biomarkers that reflect heterogeneous landscapes of the TME. Methods and materials Based upon the ESTIMATE algorithm, we evaluated the infiltrating levels of immune and stromal components derived from patients afflicted by various types of cancer from The Cancer Genome Atlas database (TCGA). According to respective patient immune and stromal scores, we categorized cases into high‐ and low‐scoring subgroups for each cancer type to explore associations between TME and patient prognosis. Gene Set Enrichment Analyses (GSEA) were conducted and genes enriched in IFNγ response signaling pathway were selected to facilitate establishment of a risk model for predicting overall survival (OS). Furthermore, we investigated the associations between the prognostic signature and tumor immune infiltration landscape by using CIBERSORT algorithm and TIMER database. Results Among the cancers assessed, the immune scores for skin cutaneous melanoma (SKCM) were the most significantly correlated with patients' survival time (P < .0001). We identified and validated a five‐IFNγ response‐related gene signature (UBE2L6, PARP14, IFIH1, IRF2, and GBP4), which was closely correlated with the prognosis for SKCM afflicted patients. Multivariate Cox regression analysis indicated that this risk model was an independent prognostic factor for SKCM. Tumor‐infiltrating lymphocytes and specific immune checkpoint molecules had notably differential levels of expression in high‐ compared to low‐risk samples. Conclusion In this study, we established a novel five‐IFNγ response‐related gene signature that provided a better and increasingly comprehensive understanding of tumor immune landscape, and which demonstrated good performance in predicting outcomes for patients afflicted by SKCM.

BackgroundLung adenocarcinoma (LUAD) is the most common diagnostic histologic subtype of non-small cell lung cancer, but the role of receptor-type tyrosine-protein phosphatase-like N (PTPRN) in LUAD has not been studied.MethodsWe conducted a bioinformatic analysis to identify the expression of PTPRN on LUAD data from the Cancer Genome Atlas (TCGA) and the relationship between PTPRN and overall survival of LUAD patients. The effects of PTPRN on the migration ability of LUAD cells and the underlying mechanisms were investigated by in vitro and in vivo assays (i.e., wound healing assay, transwell assay, western blotting, xenograft model, and immunohistochemistry). Gene-set enrichment analysis and computational resource were used to analyze the correlation between PTPRN and different tumor-infiltrating immune cells (TIICs). Lactate dehydrogenase assay and Enzyme-linked immunosorbent assay were conducted to examine natural killer (NK) cell cytotoxicity.ResultsIn our study, we found that PTPRN was up-regulated in LUAD and related to metastasis of LUAD patients. Besides, PTPRN was correlated with poor prognosis in the TCGA-LUAD dataset. PTPRN overexpression promoted LUAD cell migration and the expression of EMT markers by influencing MEK/ERK and PI3K/AKT signaling. Moreover, PTPRN expression was significantly associated with TIICs, especially NK cells. A549 and H1299 cells overexpressed PTPRN inhibited NK cell cytotoxicity.ConclusionTaken together, these findings demonstrated that PTPRN might be a potential and novel therapeutic target modulating antitumor immune response in treatment of LUAD.