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Background Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood.Methodology/Principal Findings89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant ΔsalKR restored its soaring pathogenicity. Colonization experiments showed that the ΔsalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the ΔsalKR mutant.Conclusions/SignificanceThese findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.

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The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumour formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of downstream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in HeLa and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in HeLa and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers.

BackgroundWilms’ tumor 1-associating protein (WTAP) plays an important role in physiological processes and the development of tumor such as cell cycle regulation. The regulation of cell cycle is mainly dependent on cyclins and cyclin-dependent protein kinases (CDKs). Recent studies have shown that CDKs are closely related to the tumor diagnosis, progression and response to treatment. However, their specific biological roles and related mechanism in renal cell carcinoma (RCC) remain unknown.MethodsQuantitative real-time PCR, western blotting and immunohistochemistry were used to detect the expression of WTAP and CDK2. The survival analysis was adopted to explore the association between WTAP expression and the prognosis of RCC. Cells were stably transfected with lentivirus approach and cell proliferation and cell cycle, as well as tumorigenesis in nude mice were performed to assess the effect of WTAP in RCC. RNA immunoprecipitation, Luciferase reporter assay and siRNA were employed to identify the direct binding sites of WTAP with CDK2 transcript. Colony formation assay was conducted to confirm the function of CDK2 in WTAP-induced growth promoting.ResultsIn RCC cell lines and tissues, WTAP was significantly over-expressed. Compared with patients with low expression of WTAP, patients with high expression of WTAP had lower overall survival rate. Additionally, cell function test indicated that cell proliferation abilities in WTAP over-expressed group were enhanced, while WTAP knockdown showed the opposite results. Subcutaneous xenograft tumor model displayed that knockdown of WTAP could impede tumorigenesis in vivo. Mechanism study exhibited that CDK2 expression was positively associated with the expression of WTAP. Moreover, WTAP stabilized CDK2 transcript to enhance CDK2 expression via binding to 3′-UTR of CDK2 transcript. Additionally, specific inhibitors of CDK2 activity and small interfering RNA (siRNA) of CDK2 expression inhibited WTAP-mediated promotion of proliferation.ConclusionsThese findings suggest that WTAP may have an oncogenic role in RCC through physically binding to CDK2 transcript and enhancing its transcript stability which might provide new insights into RCC therapy.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0706-6) contains supplementary material, which is available to authorized users.

Background: Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear.

Background: Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer.

Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.