Non‐coding RNA 886 (nc886/VTRNA2‐1) is a Pol III transcript and an atypical imprinted gene. Its exact function as a negative regulator of protein kinase R establishes its connection with innate immunity. Studies have shown that nc886 silencing is closely associated with prostate cancer progression. Previous work has constructed a cell model of stable nc886 overexpression (“mimic” or “nc886 + ”) in PC‐3M‐1E8 cell lines (1E8), which are highly bone‐metastatic human prostate cancer cells with low expression of nc886, and cells expressing the mimic were validated to have lower invasive and metastatic abilities than cells expressing the scramble transcript in vitro and in vivo. In this study, we directly injected mimic or scramble cells into the left ventricle of C57BL/C mice, an immunocompetent animal model, to elucidate the immune mechanisms of tumor‐host interactions. Interestingly, we found that tumor cells induced the inflammation of many important organs due to xenogeneic antigen rejection; this inflammation was ultimately repaired by tissue fibrosis after 28 days, except for in the spleen. The reason is that mimic cells, as heterogeneous antigens, are mostly directly recognized by macrophages or T cells in blood, and few mimic cells enter the spleen compared with scramble cells. The induction of splenic macrophage polarization to M2 macrophages by scramble cells is a critical factor in maintaining chronic splenic inflammation. In addition, we recognize that nc886 broadly decreases the expression of some human leukocyte antigen molecules and antigen transporters. This evidence reveals the interesting role of nc886 in regulating tumor cell antigens.

The major cause of mortality for prostate cancer (PCa) is metastasis; however, the metastatic mechanism remains unclear. MicroRNAs (miRNAs) alter the expression patterns of essential genes through posttranscriptional regulation during cancer development. The study was mainly aimed at identifying specific miRNA‐messenger RNA (mRNA) interactions and signaling pathways associated with PCa distant metastasis. New analytical approaches were applied, combining miRNA and gene expression microarray, to screen differentially expressed miRNA‐mRNA pairs in the normal prostate epithelial cell line RWPE‐1, the highly‐metastatic human PCa cell line PC‐3M‐1E8 (H‐1E8 or 1E8) and the lowly metastatic cell line PC‐3M‐2B4 (L‐2B4 or 2B4). Eight differentially expressed candidate miRNAs and their targets closely related to PCa metastasis were identified and validated in patients by using the Gene Expression Omnibus database. Among them, overexpression of hsa‐miR‐92b‐3p and hsa‐let‐7a‐5p and underexpression of their targets, such as glutathione‐S‐transferase M3 (GSTM3), baculoviral IAP repeat‐containing 3, and cyclin‐dependent kinase inhibitor 1 (CDKN1A), were also validated in H‐1E8 cells compared with L‐2B4 cells. Bioinformatics suggested that hsa‐miR‐92b‐3p and hsa‐let‐7a‐5p and their targets might promote PCa metastasis through platinum‐based drug resistance and the JAK‐STAT signaling pathway. H‐1E8 and L‐2B4 cells treated by cisplatin showed the greatly decreased levels of hsa‐miR‐92b‐3p and hsa‐let‐7a‐5p; however, in contrast to 2B4 cells, 1E8 cells did not negatively regulate the increase in the expression levels of the targets GSTM3 and CDKN1A. This finding suggests that the dysregulation between hsa‐let‐7a‐5p/CDKN1A and hsa‐miR‐92b‐3p/GSTM3 pairs is associated with platinum‐based chemoresistance of metastatic cancer cells.