MicroRNAs (miRNAs) play important roles in human diseases, such as cancer. Human miRNA-7-5p is a tumor suppressor miRNA that inhibits tumor growth by regulating multiple oncogenic signal pathways. Recently, studies revealed that plant miRNAs could regulate mammalian gene expression in a cross-kingdom manner. Schistosoma japonicum miRNA-7-5p (designated as sja-miR-7-5p) is conserved between the parasites and mammals. Thus, we investigated whether sja-miR-7-5p has similar antitumor activity to its mammalian counterpart. We first showed that sja-miR-7-5p was detected in host hepatocytes during S. japonicum infection. The sja-miR-7-5p mimics significantly inhibited the growth, migration, and colony formation of mouse and human hepatoma cell lines in vitro , and induced G1/G0 cell cycle arrest. In a xenograft animal model, the tumor volume and weight were significantly reduced in mice inoculated with hepatoma cells transfected with sja-miR-7-5p mimics compared with those transfected with NC miRNAs. Furthermore, the antitumor activity of sja-miR-7-5p was suggested by cross-species downregulation of the S-phase kinase-associated protein 2 gene in the host. Thus, sja-miR-7-5p is translocated into hepatocytes and exerts its anti-cancer activities in mammals, implying that sja-miR-7-5p might strengthen host resistance to hepatocellular carcinoma during schistosome infection.

Schistosoma japonicum eggs trapped in host liver secretes microRNA (miRNA)-containing extracellular vesicles (EVs) that can be transferred to host cells. Recent studies demonstrated that miRNAs derived from plants can modulate gene expression and phenotype of mammalian cells in a cross-kingdom manner. In this study, we identified a Schistosoma japonicum miRNA (e.g., Sja-miR-3096) that is present in the hepatocytes of mice infected with the parasite and has notable antitumor effects in both in vitro and in vivo models. The Sja-miR-3096 mimics suppressed cell proliferation and migration of both murine and human hepatoma cell lines by targeting phosphoinositide 3-kinase class II alpha (PIK3C2A). We generated a murine hepatoma cell line that stably expressed the pri-Sja-miR-3096 gene and demonstrated cross-species processing of the schistosome pri-miRNA to the mature Sja-miR-3096 in the mammalian cell. Importantly, inoculation of this cell line into the scapula and livers of mice led to a complete suppression of tumorigenesis of the hepatoma cells. Moreover, tumor weight was significantly reduced on intravenous administration of Sja-miR-3096 mimics. Thus, the schistosome miRNA-mediated antitumor activity occurs in host liver cells during schistosome infection, which may strengthen resistance of host to liver cancer, and discovery and development of such miRNAs may present promising interventions for cancer therapy.

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Schistosomiasis japonica is one of the most prevalent parasitic diseases in China. The scarcity of effective diagnostic tools is a major factor that contributes to the high prevalence of schistosomiasis japonica. SjSP-13 is a promising serological diagnostic biomarker of the disease. However, it is unclear whether polymorphisms in SjSP-13 affect its diagnostic efficacy and immunogenicity. Here, we found the SjSP-13 gene was highly polymorphic, and all the alleles of the gene were clustered into two clades, clade A and B. SjSP-13.6 and SjSP-13.25, the representative alleles of clade A and B, were produced in Escherichia coli. The diagnostic value of SjSP-13.6 (AUC = 0.983 ± 0.006), was found to be similar to the SjSP-13.25 (AUC = 0.973 ± 0.009) by receiver operating characteristic (ROC) analysis. SjSP-13.6 and SjSP-13.25 have the same specificity (96.7%), while the sensitivity of SjSP-13.6 (90.4%) is slightly but not significantly higher than SjSP-13.25 (85.2%). The combination use of the two alleles (SjSP-13.6/25) didn’t increase the diagnostic performance of SjSP-13 as the AUC value of SjSP-13.6/25 is 0.977 ± 0.009, lower than individual SjSP-13.6 (AUC = 0.983 ± 0.006). In addition, we found the immunogenicity of clade A alleles is significantly higher than clade B in Schistosoma japonicum naturally infected animals and patients, as the mean antibody levels of SjSP-13.6 was significantly higher than SjSP-13.25. We conclude that polymorphisms of the SjSP-13 gene should not affect its diagnostic efficacy, and it is not necessary to combine the alleles of the two clades for diagnosis of schistosomiasis.

MicroRNA (miRNA) is an important regulator for gene expression. Recent studies showed that some heterogenous miRNAs derived from both parasite and plant can regulate expression of mammalian gene in a cross-species or even a cross-kingdom manner. Here, we identified a Schistosoma japonicum miRNA (designated as sja-miR-61) that is present in the hepatocyte of mice infected with the parasite. The sja-miR-61 mimics significantly inhibited the migration of both mouse and human hepatoma cells in vitro. In a xenograft animal model, significant reductions of the tumor volume and weight were observed in mice inoculated with hepatoma cells transfected with sja-miR-61 mimics compared to the controls. We found that the in vivo inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 (PGAM1) gene as a target of sja-miR-61 and found that the sja-miR-61-mediated suppression of cell migration and anti-angiogenesis by cross-species down-regulation of PGAM1 expression. These data indicated that sja-miR-61 is a tumor suppressor miRNA that may have therapeutic potential for human cancers.

The complete mitochondrial genome was sequenced from the toad-headed viviparous lizard subspecies, Phrynocephalus erythrurus parva, which occupies the highest regions of any reptile on the earth. The mitogenome sequence was 16,431 bp in size, with the overall base composition of H-strand is T: 26.06%, C: 25.14%, A: 36.45%, G: 12.35%. It consists of 13 protein coding, 22 tRNA, 2 rRNA genes and 3 control regions, and its gene order and gene content were identical with the published congeneric mitogenomes of other Phrynocephalus, except for the small protion between tRNA-Pro and tRNA-Phe.

Background: Calcium-dependent protein kinases (CDPKs) play important roles both in developments and response to stresses, via mediating Ca2+ signal transduction in plants. To characterize the CDPKs in apple (Malus domestica), the apple CDPK gene family, together with those from pear (Pyrus bretschneideri), peach (Prunus persica), strawberry (Fragaria vesca), and and Arabidopsis thaliana, were analyzed at the genome-wide level in the present study.Results: A total of 116 CDPKs, consisting of 24 MdCDPKs, 28 PbCDPKs, 16 PpCDPKs, 14 FvCDPKs, and 34 AtCDPKs, was identified from apple, pear, peach, strawberry, and Arabidopsis, respectively. An integrated analysis of these CDPKs was performed on their chromosomal distribution, phylogenetic and collinearity relationships, characteristics of gene structures and conserved motifs. As a result, the CDPK gene family members were showed to be highly conserved both at their kinase and EF-hand domains. Among 209 gene-pairs with interspecies collinearity, there existed 22, 36, 21, and 25 ones between MdCDPKs and other CDPKs in Arabidopsis, pear, strawberry, and peach, respectively. And the evaluated Ka/Ks ratios were less than 1 between the CDPK gene pairs with collinearity relationships. Transcriptomic analysis demonstrated that among 24 members of the apple CDPK gene family, two up-regulatory ones (HF05266 and HF09216) and two down-regulatory ones (HF05471 and HF15429), were differentially expressed with significance between the apple fruit developmental stage S4 (mature) and other stages (early growing-S1, mid growing-S2, and late growing-S3), respectively.Conclusions: The whole genome duplication and subsequent purifying selection, might have played an important role in the CDPK gene expansion, leading to structural and functional novelty during evolution of the species lineages. In many cases, the MdCDPK genes within a phylogenetic group could show the different expression patterns at the transcriptional level, suggesting that these MdCDPKs have undergone genetic variant events and potential functional diversification. Some of MdCDPKs with significantly differential expression, were indicated their particular functions at the specific stages of apple fruit development.